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Psychiatric behaviors associated with cytoskeletal defects in radial neuronal migration

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Abstract

Normal development of the cerebral cortex is an important process for higher brain functions, such as language, and cognitive and social functions. Psychiatric disorders, such as schizophrenia and autism, are thought to develop owing to various dysfunctions occurring during the development of the cerebral cortex. Radial neuronal migration in the embryonic cerebral cortex is a complex process, which is achieved by strict control of cytoskeletal dynamics, and impairments in this process are suggested to cause various psychiatric disorders. Our recent findings indicate that radial neuronal migration as well as psychiatric behaviors is rescued by controlling microtubule stability during the embryonic stage. In this review, we outline the relationship between psychiatric disorders, such as schizophrenia and autism, and radial neuronal migration in the cerebral cortex by focusing on the cytoskeleton and centrosomes. New treatment strategies for psychiatric disorders will be discussed.

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References

  1. Wozniak RH, Leezenbaum NB, Northrup JB, West KL, Iverson JM (2017) The development of autism spectrum disorders: variability and causal complexity. Wiley Interdiscip Rev Cogn Sci. doi:10.1002/wcs.1426

    PubMed  Google Scholar 

  2. Budday S, Steinmann P, Kuhl E (2015) Physical biology of human brain development. Front Cell Neurosci 9:257. doi:10.3389/fncel.2015.00257

    Article  PubMed  PubMed Central  Google Scholar 

  3. McOmish CE, Burrows EL, Hannan AJ (2014) Identifying novel interventional strategies for psychiatric disorders: integrating genomics, ‘enviromics’ and gene–environment interactions in valid preclinical models. Br J Pharmacol 171(20):4719–4728. doi:10.1111/bph.12783

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Stolp H, Neuhaus A, Sundramoorthi R, Molnar Z (2012) The long and the short of it: gene and environment interactions during early cortical development and consequences for long-term neurological disease. Front Psychiatry 3:50. doi:10.3389/fpsyt.2012.00050

    Article  PubMed  PubMed Central  Google Scholar 

  5. Tsuang MT, Bar JL, Stone WS, Faraone SV (2004) Gene–environment interactions in mental disorders. World Psychiatry 3(2):73–83

    PubMed  PubMed Central  Google Scholar 

  6. Beckmann H (1999) Developmental malformations in cerebral structures of schizophrenic patients. Eur Arch Psychiatry Clin Neurosci 249(Suppl 4):44–47

    Article  PubMed  Google Scholar 

  7. Akbarian S, Kim JJ, Potkin SG, Hetrick WP, Bunney WE Jr, Jones EG (1996) Maldistribution of interstitial neurons in prefrontal white matter of the brains of schizophrenic patients. Arch Gen Psychiatry 53(5):425–436

    Article  CAS  PubMed  Google Scholar 

  8. Falkai P, Schneider-Axmann T, Honer WG (2000) Entorhinal cortex pre-alpha cell clusters in schizophrenia: quantitative evidence of a developmental abnormality. Biol Psychiatry 47(11):937–943

    Article  CAS  PubMed  Google Scholar 

  9. Arnold SE, Hyman BT, Van Hoesen GW, Damasio AR (1991) Some cytoarchitectural abnormalities of the entorhinal cortex in schizophrenia. Arch Gen Psychiatry 48(7):625–632

    Article  CAS  PubMed  Google Scholar 

  10. Jakob H, Beckmann H (1986) Prenatal developmental disturbances in the limbic allocortex in schizophrenics. J Neural Transm 65(3–4):303–326

    Article  CAS  PubMed  Google Scholar 

  11. Ehrlich S, Brauns S, Yendiki A, Ho BC, Calhoun V, Schulz SC, Gollub RL, Sponheim SR (2012) Associations of cortical thickness and cognition in patients with schizophrenia and healthy controls. Schizophr Bull 38(5):1050–1062. doi:10.1093/schbul/sbr018

    Article  PubMed  Google Scholar 

  12. Chance SA, Tzotzoli PM, Vitelli A, Esiri MM, Crow TJ (2004) The cytoarchitecture of sulcal folding in Heschl’s sulcus and the temporal cortex in the normal brain and schizophrenia: lamina thickness and cell density. Neurosci Lett 367(3):384–388. doi:10.1016/j.neulet.2004.06.041

    Article  CAS  PubMed  Google Scholar 

  13. Beasley CL, Cotter DR, Everall IP (2002) Density and distribution of white matter neurons in schizophrenia, bipolar disorder and major depressive disorder: no evidence for abnormalities of neuronal migration. Mol Psychiatry 7(6):564–570. doi:10.1038/sj.mp.4001038

    Article  CAS  PubMed  Google Scholar 

  14. Krimer LS, Herman MM, Saunders RC, Boyd JC, Hyde TM, Carter JM, Kleinman JE, Weinberger DR (1997) A qualitative and quantitative analysis of the entorhinal cortex in schizophrenia. Cereb Cortex 7(8):732–739

    Article  CAS  PubMed  Google Scholar 

  15. Akil M, Lewis DA (1997) Cytoarchitecture of the entorhinal cortex in schizophrenia. Am J Psychiatry 154(7):1010–1012. doi:10.1176/ajp.154.7.1010

    Article  CAS  PubMed  Google Scholar 

  16. Casanova MF (2014) Autism as a sequence: from heterochronic germinal cell divisions to abnormalities of cell migration and cortical dysplasias. Med Hypotheses 83(1):32–38. doi:10.1016/j.mehy.2014.04.014

    Article  PubMed  PubMed Central  Google Scholar 

  17. Bailey A, Luthert P, Dean A, Harding B, Janota I, Montgomery M, Rutter M, Lantos P (1998) A clinicopathological study of autism. Brain 121(Pt 5):889–905

    Article  PubMed  Google Scholar 

  18. Bauman M, Kemper TL (1985) Histoanatomic observations of the brain in early infantile autism. Neurology 35(6):866–874

    Article  CAS  PubMed  Google Scholar 

  19. Hutsler JJ, Love T, Zhang H (2007) Histological and magnetic resonance imaging assessment of cortical layering and thickness in autism spectrum disorders. Biol Psychiatry 61(4):449–457. doi:10.1016/j.biopsych.2006.01.015

    Article  PubMed  Google Scholar 

  20. Penzes P, Cahill ME, Jones KA, VanLeeuwen JE, Woolfrey KM (2011) Dendritic spine pathology in neuropsychiatric disorders. Nat Neurosci 14(3):285–293. doi:10.1038/nn.2741/nn.2741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hutsler JJ, Zhang H (2010) Increased dendritic spine densities on cortical projection neurons in autism spectrum disorders. Brain Res 1309:83–94. doi:10.1016/j.brainres.2009.09.120

    Article  CAS  PubMed  Google Scholar 

  22. Irwin SA, Patel B, Idupulapati M, Harris JB, Crisostomo RA, Larsen BP, Kooy F, Willems PJ, Cras P, Kozlowski PB, Swain RA, Weiler IJ, Greenough WT (2001) Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination. Am J Med Genet 98(2):161–167

    Article  CAS  PubMed  Google Scholar 

  23. Girirajan S, Dennis MY, Baker C, Malig M, Coe BP, Campbell CD, Mark K, Vu TH, Alkan C, Cheng Z, Biesecker LG, Bernier R, Eichler EE (2013) Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder. Am J Hum Genet 92(2):221–237. doi:10.1016/j.ajhg.2012.12.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Sanders SJ, Murtha MT, Gupta AR, Murdoch JD, Raubeson MJ, Willsey AJ, Ercan-Sencicek AG, DiLullo NM, Parikshak NN, Stein JL, Walker MF, Ober GT, Teran NA, Song Y, El-Fishawy P, Murtha RC, Choi M, Overton JD, Bjornson RD, Carriero NJ, Meyer KA, Bilguvar K, Mane SM, Sestan N, Lifton RP, Gunel M, Roeder K, Geschwind DH, Devlin B, State MW (2012) De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature 485(7397):237–241. doi:10.1038/nature10945

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Levy D, Ronemus M, Yamrom B, Lee YH, Leotta A, Kendall J, Marks S, Lakshmi B, Pai D, Ye K, Buja A, Krieger A, Yoon S, Troge J, Rodgers L, Iossifov I, Wigler M (2011) Rare de novo and transmitted copy-number variation in autistic spectrum disorders. Neuron 70(5):886–897. doi:10.1016/j.neuron.2011.05.015

    Article  CAS  PubMed  Google Scholar 

  26. Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, Walsh T, Yamrom B, Yoon S, Krasnitz A, Kendall J, Leotta A, Pai D, Zhang R, Lee YH, Hicks J, Spence SJ, Lee AT, Puura K, Lehtimaki T, Ledbetter D, Gregersen PK, Bregman J, Sutcliffe JS, Jobanputra V, Chung W, Warburton D, King MC, Skuse D, Geschwind DH, Gilliam TC, Ye K, Wigler M (2007) Strong association of de novo copy number mutations with autism. Science 316(5823):445–449. doi:10.1126/science.1138659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Turner TN, Hormozdiari F, Duyzend MH, McClymont SA, Hook PW, Iossifov I, Raja A, Baker C, Hoekzema K, Stessman HA, Zody MC, Nelson BJ, Huddleston J, Sandstrom R, Smith JD, Hanna D, Swanson JM, Faustman EM, Bamshad MJ, Stamatoyannopoulos J, Nickerson DA, McCallion AS, Darnell R, Eichler EE (2016) Genome sequencing of autism-affected families reveals disruption of putative noncoding regulatory DNA. Am J Hum Genet 98(1):58–74. doi:10.1016/j.ajhg.2015.11.023

    Article  CAS  PubMed  Google Scholar 

  28. Yuen RK, Thiruvahindrapuram B, Merico D, Walker S, Tammimies K, Hoang N, Chrysler C, Nalpathamkalam T, Pellecchia G, Liu Y, Gazzellone MJ, D’Abate L, Deneault E, Howe JL, Liu RS, Thompson A, Zarrei M, Uddin M, Marshall CR, Ring RH, Zwaigenbaum L, Ray PN, Weksberg R, Carter MT, Fernandez BA, Roberts W, Szatmari P, Scherer SW (2015) Whole-genome sequencing of quartet families with autism spectrum disorder. Nat Med 21(2):185–191. doi:10.1038/nm.3792

    Article  CAS  PubMed  Google Scholar 

  29. Lo-Castro A, Curatolo P (2014) Epilepsy associated with autism and attention deficit hyperactivity disorder: is there a genetic link? Brain Dev 36(3):185–193. doi:10.1016/j.braindev.2013.04.013

    Article  PubMed  Google Scholar 

  30. Taurines R, Schwenck C, Westerwald E, Sachse M, Siniatchkin M, Freitag C (2012) ADHD and autism: differential diagnosis or overlapping traits? A selective review. Atten Defic Hyperact Disord 4(3):115–139. doi:10.1007/s12402-012-0086-2

    Article  PubMed  Google Scholar 

  31. Thapar A, Cooper M, Rutter M (2016) Neurodevelopmental disorders. Lancet Psychiatry. doi:10.1016/S2215-0366(16)30376-5

    PubMed Central  Google Scholar 

  32. Lyall K, Croen L, Daniels J, Fallin MD, Ladd-Acosta C, Lee BK, Park BY, Snyder NW, Schendel D, Volk HE, Windham GC, Newschaffer C (2016) The changing epidemiology of autism spectrum disorders. Annu Rev Public Health. doi:10.1146/annurev-publhealth-031816-044318

    PubMed  Google Scholar 

  33. Gandal MJ, Leppa V, Won H, Parikshak NN, Geschwind DH (2016) The road to precision psychiatry: translating genetics into disease mechanisms. Nat Neurosci 19(11):1397–1407. doi:10.1038/nn.4409

    Article  CAS  PubMed  Google Scholar 

  34. Schork AJ, Wang Y, Thompson WK, Dale AM, Andreassen OA (2016) New statistical approaches exploit the polygenic architecture of schizophrenia—implications for the underlying neurobiology. Curr Opin Neurobiol 36:89–98. doi:10.1016/j.conb.2015.10.008

    Article  CAS  PubMed  Google Scholar 

  35. Wallace R (2016) Environmental induction of neurodevelopmental disorders. Bull Math Biol 78(12):2408–2426. doi:10.1007/s11538-016-0226-5

    Article  CAS  PubMed  Google Scholar 

  36. Attademo L, Bernardini F, Garinella R, Compton MT (2017) Environmental pollution and risk of psychotic disorders: a review of the science to date. Schizophr Res 181:55–59. doi:10.1016/j.schres.2016.10.003

    Article  PubMed  Google Scholar 

  37. Modabbernia A, Velthorst E, Reichenberg A (2017) Environmental risk factors for autism: an evidence-based review of systematic reviews and meta-analyses. Mol Autism 8:13. doi:10.1186/s13229-017-0121-4

    Article  PubMed  PubMed Central  Google Scholar 

  38. Gaugler T, Klei L, Sanders SJ, Bodea CA, Goldberg AP, Lee AB, Mahajan M, Manaa D, Pawitan Y, Reichert J, Ripke S, Sandin S, Sklar P, Svantesson O, Reichenberg A, Hultman CM, Devlin B, Roeder K, Buxbaum JD (2014) Most genetic risk for autism resides with common variation. Nat Genet 46(8):881–885. doi:10.1038/ng.3039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Baron-Cohen S (2002) The extreme male brain theory of autism. Trends Cogn Sci 6(6):248–254

    Article  PubMed  Google Scholar 

  40. Brosnan M, Ashwin C, Walker I, Donaghue J (2010) Can an ‘extreme female brain’ be characterised in terms of psychosis? Personal Individ Differ 49(7):738–742. doi:10.1016/j.paid.2010.06.018

    Article  Google Scholar 

  41. Penagarikano O, Abrahams BS, Herman EI, Winden KD, Gdalyahu A, Dong H, Sonnenblick LI, Gruver R, Almajano J, Bragin A, Golshani P, Trachtenberg JT, Peles E, Geschwind DH (2011) Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits. Cell 147(1):235–246. doi:10.1016/j.cell.2011.08.040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Chen T, Wu Q, Zhang Y, Zhang D (2015) NDUFV2 regulates neuronal migration in the developing cerebral cortex through modulation of the multipolar–bipolar transition. Brain Res 1625:102–110. doi:10.1016/j.brainres.2015.08.028

    Article  CAS  PubMed  Google Scholar 

  43. Lee FH, Fadel MP, Preston-Maher K, Cordes SP, Clapcote SJ, Price DJ, Roder JC, Wong AH (2011) Disc1 point mutations in mice affect development of the cerebral cortex. J Neurosci 31(9):3197–3206. doi:10.1523/JNEUROSCI.4219-10.2011

    Article  CAS  PubMed  Google Scholar 

  44. La Fata G, Gartner A, Dominguez-Iturza N, Dresselaers T, Dawitz J, Poorthuis RB, Averna M, Himmelreich U, Meredith RM, Achsel T, Dotti CG, Bagni C (2014) FMRP regulates multipolar to bipolar transition affecting neuronal migration and cortical circuitry. Nat Neurosci 17(12):1693–1700. doi:10.1038/nn.3870

    Article  PubMed  CAS  Google Scholar 

  45. Cunningham CL, Martinez Cerdeno V, Navarro Porras E, Prakash AN, Angelastro JM, Willemsen R, Hagerman PJ, Pessah IN, Berman RF, Noctor SC (2011) Premutation CGG-repeat expansion of the Fmr1 gene impairs mouse neocortical development. Hum Mol Genet 20(1):64–79. doi:10.1093/hmg/ddq432

    Article  CAS  PubMed  Google Scholar 

  46. Cooper JA (2013) Cell biology in neuroscience: mechanisms of cell migration in the nervous system. J Cell Biol 202(5):725–734. doi:10.1083/jcb.201305021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Jiang X, Nardelli J (2016) Cellular and molecular introduction to brain development. Neurobiol Dis 92(Pt A):3–17. doi:10.1016/j.nbd.2015.07.007

    Article  CAS  PubMed  Google Scholar 

  48. Bystron I, Blakemore C, Rakic P (2008) Development of the human cerebral cortex: boulder committee revisited. Nat Rev Neurosci 9(2):110–122. doi:10.1038/nrn2252

    Article  CAS  PubMed  Google Scholar 

  49. Marin-Padilla M (1971) Early prenatal ontogenesis of the cerebral cortex (neocortex) of the cat (Felis domestica). A Golgi study. I. The primordial neocortical organization. Z Anat Entwicklungsgesch 134(2):117–145

    Article  CAS  PubMed  Google Scholar 

  50. Metin C, Vallee RB, Rakic P, Bhide PG (2008) Modes and mishaps of neuronal migration in the mammalian brain. J Neurosci 28(46):11746–11752. doi:10.1523/JNEUROSCI.3860-08.2008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Rakic P (2003) Developmental and evolutionary adaptations of cortical radial glia. Cereb Cortex 13(6):541–549

    Article  PubMed  Google Scholar 

  52. Marin O, Rubenstein JL (2003) Cell migration in the forebrain. Annu Rev Neurosci 26:441–483. doi:10.1146/annurev.neuro.26.041002.131058

    Article  CAS  PubMed  Google Scholar 

  53. Tabata H, Nakajima K (2003) Multipolar migration: the third mode of radial neuronal migration in the developing cerebral cortex. J Neurosci 23(31):9996–10001

    CAS  PubMed  Google Scholar 

  54. Nadarajah B, Brunstrom JE, Grutzendler J, Wong RO, Pearlman AL (2001) Two modes of radial migration in early development of the cerebral cortex. Nat Neurosci 4(2):143–150. doi:10.1038/83967

    Article  CAS  PubMed  Google Scholar 

  55. Tabata H, Kanatani S, Nakajima K (2009) Differences of migratory behavior between direct progeny of apical progenitors and basal progenitors in the developing cerebral cortex. Cereb Cortex 19(9):2092–2105. doi:10.1093/cercor/bhn227

    Article  PubMed  Google Scholar 

  56. Nadarajah B, Parnavelas JG (2002) Modes of neuronal migration in the developing cerebral cortex. Nat Rev Neurosci 3(6):423–432. doi:10.1038/nrn845

    Article  CAS  PubMed  Google Scholar 

  57. Schaar BT, McConnell SK (2005) Cytoskeletal coordination during neuronal migration. Proc Natl Acad Sci USA 102(38):13652–13657. doi:10.1073/pnas.0506008102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Kawauchi T (2015) Cellullar insights into cerebral cortical development: focusing on the locomotion mode of neuronal migration. Front Cell Neurosci 9:394. doi:10.3389/fncel.2015.00394

    Article  PubMed  PubMed Central  Google Scholar 

  59. Ayala R, Shu T, Tsai LH (2007) Trekking across the brain: the journey of neuronal migration. Cell 128(1):29–43. doi:10.1016/j.cell.2006.12.021

    Article  CAS  PubMed  Google Scholar 

  60. Hansen DV, Lui JH, Parker PR, Kriegstein AR (2010) Neurogenic radial glia in the outer subventricular zone of human neocortex. Nature 464(7288):554–561. doi:10.1038/nature08845

    Article  CAS  PubMed  Google Scholar 

  61. Rakic P (1974) Neurons in rhesus monkey visual cortex: systematic relation between time of origin and eventual disposition. Science 183(4123):425–427

    Article  CAS  PubMed  Google Scholar 

  62. Rakic P, Sidman RL (1968) Subcommissural organ and adjacent ependyma: autoradiographic study of their origin in the mouse brain. Am J Anat 122(2):317–335. doi:10.1002/aja.1001220210

    Article  CAS  PubMed  Google Scholar 

  63. Berlucchi G (2012) Frontal callosal disconnection syndromes. Cortex 48(1):36–45. doi:10.1016/j.cortex.2011.04.008

    Article  PubMed  Google Scholar 

  64. Fame RM, MacDonald JL, Macklis JD (2011) Development, specification, and diversity of callosal projection neurons. Trends Neurosci 34(1):41–50. doi:10.1016/j.tins.2010.10.002

    Article  CAS  PubMed  Google Scholar 

  65. Nakajima K (2007) Control of tangential/non-radial migration of neurons in the developing cerebral cortex. Neurochem Int 51(2–4):121–131. doi:10.1016/j.neuint.2007.05.006

    Article  CAS  PubMed  Google Scholar 

  66. Corbin JG, Nery S, Fishell G (2001) Telencephalic cells take a tangent: non-radial migration in the mammalian forebrain. Nat Neurosci 4(Suppl):1177–1182. doi:10.1038/nn749

    Article  CAS  PubMed  Google Scholar 

  67. Maricich SM, Gilmore EC, Herrup K (2001) The role of tangential migration in the establishment of mammalian cortex. Neuron 31(2):175–178

    Article  CAS  PubMed  Google Scholar 

  68. Marin O, Rubenstein JL (2001) A long, remarkable journey: tangential migration in the telencephalon. Nat Rev Neurosci 2(11):780–790. doi:10.1038/35097509

    Article  CAS  PubMed  Google Scholar 

  69. Kuijpers M, Hoogenraad CC (2011) Centrosomes, microtubules and neuronal development. Mol Cell Neurosci 48(4):349–358. doi:10.1016/j.mcn.2011.05.004

    Article  CAS  PubMed  Google Scholar 

  70. Liu JS (2011) Molecular genetics of neuronal migration disorders. Curr Neurol Neurosci Rep 11(2):171–178. doi:10.1007/s11910-010-0176-5

    Article  CAS  PubMed  Google Scholar 

  71. Kawauchi T, Hoshino M (2008) Molecular pathways regulating cytoskeletal organization and morphological changes in migrating neurons. Dev Neurosci 30(1–3):36–46. doi:10.1159/000109850

    CAS  PubMed  Google Scholar 

  72. Tsai JW, Bremner KH, Vallee RB (2007) Dual subcellular roles for LIS1 and dynein in radial neuronal migration in live brain tissue. Nat Neurosci 10(8):970–979. doi:10.1038/nn1934

    Article  CAS  PubMed  Google Scholar 

  73. Coles CH, Bradke F (2015) Coordinating neuronal actin-microtubule dynamics. Curr Biol 25(15):R677–R691. doi:10.1016/j.cub.2015.06.020

    Article  CAS  PubMed  Google Scholar 

  74. Mohan R, John A (2015) Microtubule-associated proteins as direct crosslinkers of actin filaments and microtubules. IUBMB Life 67(6):395–403. doi:10.1002/iub.1384

    Article  CAS  PubMed  Google Scholar 

  75. Vallee RB, Seale GE, Tsai JW (2009) Emerging roles for myosin II and cytoplasmic dynein in migrating neurons and growth cones. Trends Cell Biol 19(7):347–355. doi:10.1016/j.tcb.2009.03.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Choi CK, Vicente-Manzanares M, Zareno J, Whitmore LA, Mogilner A, Horwitz AR (2008) Actin and alpha-actinin orchestrate the assembly and maturation of nascent adhesions in a myosin II motor-independent manner. Nat Cell Biol 10(9):1039–1050. doi:10.1038/ncb1763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Burridge K, Chrzanowska-Wodnicka M (1996) Focal adhesions, contractility, and signaling. Annu Rev Cell Dev Biol 12:463–518. doi:10.1146/annurev.cellbio.12.1.463

    Article  CAS  PubMed  Google Scholar 

  78. Vicente-Manzanares M, Ma X, Adelstein RS, Horwitz AR (2009) Non-muscle myosin II takes centre stage in cell adhesion and migration. Nat Rev Mol Cell Biol 10(11):778–790. doi:10.1038/nrm2786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Bellion A, Baudoin JP, Alvarez C, Bornens M, Metin C (2005) Nucleokinesis in tangentially migrating neurons comprises two alternating phases: forward migration of the Golgi/centrosome associated with centrosome splitting and myosin contraction at the rear. J Neurosci 25(24):5691–5699. doi:10.1523/JNEUROSCI.1030-05.2005

    Article  CAS  PubMed  Google Scholar 

  80. Yang T, Sun Y, Zhang F, Zhu Y, Shi L, Li H, Xu Z (2012) POSH localizes activated Rac1 to control the formation of cytoplasmic dilation of the leading process and neuronal migration. Cell Rep 2(3):640–651. doi:10.1016/j.celrep.2012.08.007

    Article  CAS  PubMed  Google Scholar 

  81. Xu Z, Kukekov NV, Greene LA (2003) POSH acts as a scaffold for a multiprotein complex that mediates JNK activation in apoptosis. EMBO J 22(2):252–261. doi:10.1093/emboj/cdg021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Tapon N, Nagata K, Lamarche N, Hall A (1998) A new rac target POSH is an SH3-containing scaffold protein involved in the JNK and NF-kappaB signalling pathways. EMBO J 17(5):1395–1404. doi:10.1093/emboj/17.5.1395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Solecki DJ, Trivedi N, Govek EE, Kerekes RA, Gleason SS, Hatten ME (2009) Myosin II motors and F-actin dynamics drive the coordinated movement of the centrosome and soma during CNS glial-guided neuronal migration. Neuron 63(1):63–80. doi:10.1016/j.neuron.2009.05.028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Jiang J, Zhang ZH, Yuan XB, Poo MM (2015) Spatiotemporal dynamics of traction forces show three contraction centers in migratory neurons. J Cell Biol 209(5):759–774. doi:10.1083/jcb.201410068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. He M, Zhang ZH, Guan CB, Xia D, Yuan XB (2010) Leading tip drives soma translocation via forward F-actin flow during neuronal migration. J Neurosci 30(32):10885–10898. doi:10.1523/JNEUROSCI.0240-10.2010

    Article  CAS  PubMed  Google Scholar 

  86. Li J, Cai T, Jiang Y, Chen H, He X, Chen C, Li X, Shao Q, Ran X, Li Z, Xia K, Liu C, Sun ZS, Wu J (2016) Genes with de novo mutations are shared by four neuropsychiatric disorders discovered from NP de novo database. Mol Psychiatry 21(2):290–297. doi:10.1038/mp.2015.40

    Article  PubMed  CAS  Google Scholar 

  87. Wang J, Wang Z, Liu Y, Hui L, Du W, Zhao X, Xu Y, Zhang H, Zhao X, Zhang X (2015) Lack of genetic association between the MYO9B locus and schizophrenia in a Chinese population. Psychiatr Genet 25(2):97. doi:10.1097/YPG.0000000000000072

    Article  CAS  PubMed  Google Scholar 

  88. Liu YL, Fann CS, Liu CM, Chen WJ, Wu JY, Hung SI, Chen CH, Jou YS, Liu SK, Hwang TJ, Hsieh MH, Chang CC, Yang WC, Lin JJ, Chou FH, Faraone SV, Tsuang MT, Hwu HG (2008) RASD2, MYH9, and CACNG2 genes at chromosome 22q12 associated with the subgroup of schizophrenia with non-deficit in sustained attention and executive function. Biol Psychiatry 64(9):789–796. doi:10.1016/j.biopsych.2008.04.035

    Article  CAS  PubMed  Google Scholar 

  89. Jungerius BJ, Bakker SC, Monsuur AJ, Sinke RJ, Kahn RS, Wijmenga C (2008) Is MYO9B the missing link between schizophrenia and celiac disease? Am J Med Genet B Neuropsychiatr Genet 147(3):351–355. doi:10.1002/ajmg.b.30605

    Article  PubMed  Google Scholar 

  90. Amagane H, Watanabe Y, Kaneko N, Nunokawa A, Muratake T, Ishiguro H, Arinami T, Ujike H, Inada T, Iwata N, Kunugi H, Sasaki T, Hashimoto R, Itokawa M, Ozaki N, Someya T (2010) Failure to find an association between myosin heavy chain 9, non-muscle (MYH9) and schizophrenia: a three-stage case–control association study. Schizophr Res 118(1–3):106–112. doi:10.1016/j.schres.2010.01.023

    Article  PubMed  Google Scholar 

  91. Zhao Z, Xu J, Chen J, Kim S, Reimers M, Bacanu SA, Yu H, Liu C, Sun J, Wang Q, Jia P, Xu F, Zhang Y, Kendler KS, Peng Z, Chen X (2015) Transcriptome sequencing and genome-wide association analyses reveal lysosomal function and actin cytoskeleton remodeling in schizophrenia and bipolar disorder. Mol Psychiatry 20(5):563–572. doi:10.1038/mp.2014.82

    Article  CAS  PubMed  Google Scholar 

  92. Rubio MD, Haroutunian V, Meador-Woodruff JH (2012) Abnormalities of the Duo/Ras-related C3 botulinum toxin substrate 1/p21-activated kinase 1 pathway drive myosin light chain phosphorylation in frontal cortex in schizophrenia. Biol Psychiatry 71(10):906–914. doi:10.1016/j.biopsych.2012.02.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Newell-Litwa KA, Horwitz R, Lamers ML (2015) Non-muscle myosin II in disease: mechanisms and therapeutic opportunities. Dis Model Mech 8(12):1495–1515. doi:10.1242/dmm.022103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Akhmanova A, Hoogenraad CC (2015) Microtubule minus-end-targeting proteins. Curr Biol 25(4):R162–R171. doi:10.1016/j.cub.2014.12.027

    Article  CAS  PubMed  Google Scholar 

  95. Mitchison T, Kirschner M (1984) Dynamic instability of microtubule growth. Nature 312(5991):237–242

    Article  CAS  PubMed  Google Scholar 

  96. van der Vaart B, Akhmanova A, Straube A (2009) Regulation of microtubule dynamic instability. Biochem Soc Trans 37(Pt 5):1007–1013. doi:10.1042/BST0371007

    Article  PubMed  CAS  Google Scholar 

  97. Nigg EA, Raff JW (2009) Centrioles, centrosomes, and cilia in health and disease. Cell 139(4):663–678. doi:10.1016/j.cell.2009.10.036

    Article  CAS  PubMed  Google Scholar 

  98. Pearson CG (2014) Choosing sides—asymmetric centriole and basal body assembly. J Cell Sci 127(Pt 13):2803–2810. doi:10.1242/jcs.151761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Ross L, Normark BB (2015) Evolutionary problems in centrosome and centriole biology. J Evol Biol 28(5):995–1004. doi:10.1111/jeb.12620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Wang X, Tsai JW, Imai JH, Lian WN, Vallee RB, Shi SH (2009) Asymmetric centrosome inheritance maintains neural progenitors in the neocortex. Nature 461(7266):947–955. doi:10.1038/nature08435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Tsai LH, Gleeson JG (2005) Nucleokinesis in neuronal migration. Neuron 46(3):383–388. doi:10.1016/j.neuron.2005.04.013

    Article  CAS  PubMed  Google Scholar 

  102. Higginbotham HR, Gleeson JG (2007) The centrosome in neuronal development. Trends Neurosci 30(6):276–283. doi:10.1016/j.tins.2007.04.001

    Article  CAS  PubMed  Google Scholar 

  103. Stiess M, Bradke F (2011) Neuronal polarization: the cytoskeleton leads the way. Dev Neurobiol 71(6):430–444. doi:10.1002/dneu.20849

    Article  CAS  PubMed  Google Scholar 

  104. Rivas RJ, Hatten ME (1995) Motility and cytoskeletal organization of migrating cerebellar granule neurons. J Neurosci 15(2):981–989

    CAS  PubMed  Google Scholar 

  105. Tanaka T, Serneo FF, Higgins C, Gambello MJ, Wynshaw-Boris A, Gleeson JG (2004) Lis1 and doublecortin function with dynein to mediate coupling of the nucleus to the centrosome in neuronal migration. J Cell Biol 165(5):709–721. doi:10.1083/jcb.200309025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Xie Z, Sanada K, Samuels BA, Shih H, Tsai LH (2003) Serine 732 phosphorylation of FAK by Cdk5 is important for microtubule organization, nuclear movement, and neuronal migration. Cell 114(4):469–482

    Article  CAS  PubMed  Google Scholar 

  107. Stiess M, Maghelli N, Kapitein LC, Gomis-Ruth S, Wilsch-Brauninger M, Hoogenraad CC, Tolic-Norrelykke IM, Bradke F (2010) Axon extension occurs independently of centrosomal microtubule nucleation. Science 327(5966):704–707. doi:10.1126/science.1182179

    Article  CAS  PubMed  Google Scholar 

  108. Strzyz P (2016) Post-translational modifications: extension of the tubulin code. Nat Rev Mol Cell Biol 17(10):609. doi:10.1038/nrm.2016.117

    Article  CAS  PubMed  Google Scholar 

  109. Song Y, Brady ST (2015) Post-translational modifications of tubulin: pathways to functional diversity of microtubules. Trends Cell Biol 25(3):125–136. doi:10.1016/j.tcb.2014.10.004

    Article  CAS  PubMed  Google Scholar 

  110. Janke C, Bulinski JC (2011) Post-translational regulation of the microtubule cytoskeleton: mechanisms and functions. Nat Rev Mol Cell Biol 12(12):773–786. doi:10.1038/nrm3227

    Article  CAS  PubMed  Google Scholar 

  111. Fukushima N, Furuta D, Hidaka Y, Moriyama R, Tsujiuchi T (2009) Post-translational modifications of tubulin in the nervous system. J Neurochem 109(3):683–693. doi:10.1111/j.1471-4159.2009.06013.x

    Article  CAS  PubMed  Google Scholar 

  112. LeDizet M, Piperno G (1987) Identification of an acetylation site of Chlamydomonas alpha-tubulin. Proc Natl Acad Sci USA 84(16):5720–5724

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. L’Hernault SW, Rosenbaum JL (1985) Chlamydomonas alpha-tubulin is posttranslationally modified by acetylation on the epsilon-amino group of a lysine. Biochemistry 24(2):473–478

    Article  PubMed  Google Scholar 

  114. Janke C, Kneussel M (2010) Tubulin post-translational modifications: encoding functions on the neuronal microtubule cytoskeleton. Trends Neurosci 33(8):362–372. doi:10.1016/j.tins.2010.05.001

    Article  CAS  PubMed  Google Scholar 

  115. Webster DR, Borisy GG (1989) Microtubules are acetylated in domains that turn over slowly. J Cell Sci 92(Pt 1):57–65

    PubMed  Google Scholar 

  116. Piperno G, LeDizet M, Chang XJ (1987) Microtubules containing acetylated alpha-tubulin in mammalian cells in culture. J Cell Biol 104(2):289–302

    Article  CAS  PubMed  Google Scholar 

  117. Farina F, Gaillard J, Guerin C, Coute Y, Sillibourne J, Blanchoin L, Thery M (2016) The centrosome is an actin-organizing centre. Nat Cell Biol 18(1):65–75. doi:10.1038/ncb3285

    Article  CAS  PubMed  Google Scholar 

  118. Ling H, Peng L, Seto E, Fukasawa K (2012) Suppression of centrosome duplication and amplification by deacetylases. Cell Cycle 11(20):3779–3791. doi:10.4161/cc.21985

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Shida T, Cueva JG, Xu Z, Goodman MB, Nachury MV (2010) The major alpha-tubulin K40 acetyltransferase alphaTAT1 promotes rapid ciliogenesis and efficient mechanosensation. Proc Natl Acad Sci USA 107(50):21517–21522. doi:10.1073/pnas.1013728107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Akella JS, Wloga D, Kim J, Starostina NG, Lyons-Abbott S, Morrissette NS, Dougan ST, Kipreos ET, Gaertig J (2010) MEC-17 is an alpha-tubulin acetyltransferase. Nature 467(7312):218–222. doi:10.1038/nature09324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Creppe C, Malinouskaya L, Volvert ML, Gillard M, Close P, Malaise O, Laguesse S, Cornez I, Rahmouni S, Ormenese S, Belachew S, Malgrange B, Chapelle JP, Siebenlist U, Moonen G, Chariot A, Nguyen L (2009) Elongator controls the migration and differentiation of cortical neurons through acetylation of alpha-tubulin. Cell 136(3):551–564. doi:10.1016/j.cell.2008.11.043

    Article  CAS  PubMed  Google Scholar 

  122. North BJ, Marshall BL, Borra MT, Denu JM, Verdin E (2003) The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. Mol Cell 11(2):437–444

    Article  CAS  PubMed  Google Scholar 

  123. Hubbert C, Guardiola A, Shao R, Kawaguchi Y, Ito A, Nixon A, Yoshida M, Wang XF, Yao TP (2002) HDAC6 is a microtubule-associated deacetylase. Nature 417(6887):455–458. doi:10.1038/417455a

    Article  CAS  PubMed  Google Scholar 

  124. Li L, Yang XJ (2015) Tubulin acetylation: responsible enzymes, biological functions and human diseases. Cell Mol Life Sci 72(22):4237–4255. doi:10.1007/s00018-015-2000-5

    Article  CAS  PubMed  Google Scholar 

  125. Kalebic N, Sorrentino S, Perlas E, Bolasco G, Martinez C, Heppenstall PA (2013) alphaTAT1 is the major alpha-tubulin acetyltransferase in mice. Nat Commun 4:1962. doi:10.1038/ncomms2962

    Article  PubMed  CAS  Google Scholar 

  126. Li L, Wei D, Wang Q, Pan J, Liu R, Zhang X, Bao L (2012) MEC-17 deficiency leads to reduced alpha-tubulin acetylation and impaired migration of cortical neurons. J Neurosci 32(37):12673–12683. doi:10.1523/JNEUROSCI.0016-12.2012

    Article  CAS  PubMed  Google Scholar 

  127. Kim GW, Li L, Gorbani M, You L, Yang XJ (2013) Mice lacking alpha-tubulin acetyltransferase 1 are viable but display alpha-tubulin acetylation deficiency and dentate gyrus distortion. J Biol Chem 288(28):20334–20350. doi:10.1074/jbc.M113.464792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Hawkes NA, Otero G, Winkler GS, Marshall N, Dahmus ME, Krappmann D, Scheidereit C, Thomas CL, Schiavo G, Erdjument-Bromage H, Tempst P, Svejstrup JQ (2002) Purification and characterization of the human elongator complex. J Biol Chem 277(4):3047–3052. doi:10.1074/jbc.M110445200

    Article  CAS  PubMed  Google Scholar 

  129. Kim JH, Lane WS, Reinberg D (2002) Human Elongator facilitates RNA polymerase II transcription through chromatin. Proc Natl Acad Sci USA 99(3):1241–1246. doi:10.1073/pnas.251672198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Wittschieben BO, Otero G, de Bizemont T, Fellows J, Erdjument-Bromage H, Ohba R, Li Y, Allis CD, Tempst P, Svejstrup JQ (1999) A novel histone acetyltransferase is an integral subunit of elongating RNA polymerase II holoenzyme. Mol Cell 4(1):123–128

    Article  CAS  PubMed  Google Scholar 

  131. Petrakis TG, Wittschieben BO, Svejstrup JQ (2004) Molecular architecture, structure–function relationship, and importance of the Elp3 subunit for the RNA binding of holo-elongator. J Biol Chem 279(31):32087–32092. doi:10.1074/jbc.M403361200

    Article  CAS  PubMed  Google Scholar 

  132. Zhou X, Fan LX, Li K, Ramchandran R, Calvet JP, Li X (2014) SIRT2 regulates ciliogenesis and contributes to abnormal centrosome amplification caused by loss of polycystin-1. Hum Mol Genet 23(6):1644–1655. doi:10.1093/hmg/ddt556

    Article  CAS  PubMed  Google Scholar 

  133. Southwood CM, Peppi M, Dryden S, Tainsky MA, Gow A (2007) Microtubule deacetylases, SirT2 and HDAC6, in the nervous system. Neurochem Res 32(2):187–195. doi:10.1007/s11064-006-9127-6

    Article  CAS  PubMed  Google Scholar 

  134. Jeong SG, Cho GW (2017) The tubulin deacetylase sirtuin-2 regulates neuronal differentiation through the ERK/CREB signaling pathway. Biochem Biophys Res Commun 482(1):182–187. doi:10.1016/j.bbrc.2016.11.031

    Article  CAS  PubMed  Google Scholar 

  135. Liu R, Dang W, Du Y, Zhou Q, Jiao K, Liu Z (2015) SIRT2 is involved in the modulation of depressive behaviors. Sci Rep 5:8415. doi:10.1038/srep08415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Gold WA, Lacina TA, Cantrill LC, Christodoulou J (2015) MeCP2 deficiency is associated with reduced levels of tubulin acetylation and can be restored using HDAC6 inhibitors. J Mol Med (Berl) 93(1):63–72. doi:10.1007/s00109-014-1202-x

    Article  CAS  Google Scholar 

  137. Matsuyama A, Shimazu T, Sumida Y, Saito A, Yoshimatsu Y, Seigneurin-Berny D, Osada H, Komatsu Y, Nishino N, Khochbin S, Horinouchi S, Yoshida M (2002) In vivo destabilization of dynamic microtubules by HDAC6-mediated deacetylation. EMBO J 21(24):6820–6831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Tran AD, Marmo TP, Salam AA, Che S, Finkelstein E, Kabarriti R, Xenias HS, Mazitschek R, Hubbert C, Kawaguchi Y, Sheetz MP, Yao TP, Bulinski JC (2007) HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions. J Cell Sci 120(Pt 8):1469–1479. doi:10.1242/jcs.03431

    Article  CAS  PubMed  Google Scholar 

  139. Chang CW, Hsu WB, Tsai JJ, Tang CJ, Tang TK (2016) CEP295 interacts with microtubules and is required for centriole elongation. J Cell Sci 129(13):2501–2513. doi:10.1242/jcs.186338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Zhang X, Yuan Z, Zhang Y, Yong S, Salas-Burgos A, Koomen J, Olashaw N, Parsons JT, Yang XJ, Dent SR, Yao TP, Lane WS, Seto E (2007) HDAC6 modulates cell motility by altering the acetylation level of cortactin. Mol Cell 27(2):197–213. doi:10.1016/j.molcel.2007.05.033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Kovacs JJ, Murphy PJ, Gaillard S, Zhao X, Wu JT, Nicchitta CV, Yoshida M, Toft DO, Pratt WB, Yao TP (2005) HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol Cell 18(5):601–607. doi:10.1016/j.molcel.2005.04.021

    Article  CAS  PubMed  Google Scholar 

  142. Zhang L, Liu S, Liu N, Zhang Y, Liu M, Li D, Seto E, Yao TP, Shui W, Zhou J (2015) Proteomic identification and functional characterization of MYH9, Hsc70, and DNAJA1 as novel substrates of HDAC6 deacetylase activity. Protein Cell 6(1):42–54. doi:10.1007/s13238-014-0102-8

    Article  CAS  PubMed  Google Scholar 

  143. Parmigiani RB, Xu WS, Venta-Perez G, Erdjument-Bromage H, Yaneva M, Tempst P, Marks PA (2008) HDAC6 is a specific deacetylase of peroxiredoxins and is involved in redox regulation. Proc Natl Acad Sci USA 105(28):9633–9638. doi:10.1073/pnas.0803749105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Li Y, Zhang X, Polakiewicz RD, Yao TP, Comb MJ (2008) HDAC6 is required for epidermal growth factor-induced beta-catenin nuclear localization. J Biol Chem 283(19):12686–12690. doi:10.1074/jbc.C700185200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Zhang Y, Kwon S, Yamaguchi T, Cubizolles F, Rousseaux S, Kneissel M, Cao C, Li N, Cheng HL, Chua K, Lombard D, Mizeracki A, Matthias G, Alt FW, Khochbin S, Matthias P (2008) Mice lacking histone deacetylase 6 have hyperacetylated tubulin but are viable and develop normally. Mol Cell Biol 28(5):1688–1701. doi:10.1128/MCB.01154-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Murphy PJ, Morishima Y, Kovacs JJ, Yao TP, Pratt WB (2005) Regulation of the dynamics of hsp90 action on the glucocorticoid receptor by acetylation/deacetylation of the chaperone. J Biol Chem 280(40):33792–33799. doi:10.1074/jbc.M506997200

    Article  CAS  PubMed  Google Scholar 

  147. Scroggins BT, Robzyk K, Wang D, Marcu MG, Tsutsumi S, Beebe K, Cotter RJ, Felts S, Toft D, Karnitz L, Rosen N, Neckers L (2007) An acetylation site in the middle domain of Hsp90 regulates chaperone function. Mol Cell 25(1):151–159. doi:10.1016/j.molcel.2006.12.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Fukada M, Hanai A, Nakayama A, Suzuki T, Miyata N, Rodriguiz RM, Wetsel WC, Yao TP, Kawaguchi Y (2012) Loss of deacetylation activity of Hdac6 affects emotional behavior in mice. PLoS One 7(2):e30924. doi:10.1371/journal.pone.0030924

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Jochems J, Boulden J, Lee BG, Blendy JA, Jarpe M, Mazitschek R, Van Duzer JH, Jones S, Berton O (2014) Antidepressant-like properties of novel HDAC6-selective inhibitors with improved brain bioavailability. Neuropsychopharmacology 39(2):389–400. doi:10.1038/npp.2013.207

    Article  CAS  PubMed  Google Scholar 

  150. Jochems J, Teegarden SL, Chen Y, Boulden J, Challis C, Ben-Dor GA, Kim SF, Berton O (2015) Enhancement of stress resilience through histone deacetylase 6-mediated regulation of glucocorticoid receptor chaperone dynamics. Biol Psychiatry 77(4):345–355. doi:10.1016/j.biopsych.2014.07.036

    Article  PubMed  Google Scholar 

  151. Espallergues J, Teegarden SL, Veerakumar A, Boulden J, Challis C, Jochems J, Chan M, Petersen T, Deneris E, Matthias P, Hahn CG, Lucki I, Beck SG, Berton O (2012) HDAC6 regulates glucocorticoid receptor signaling in serotonin pathways with critical impact on stress resilience. J Neurosci 32(13):4400–4416. doi:10.1523/JNEUROSCI.5634-11.2012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Poliak S, Gollan L, Martinez R, Custer A, Einheber S, Salzer JL, Trimmer JS, Shrager P, Peles E (1999) Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K+ channels. Neuron 24(4):1037–1047

    Article  CAS  PubMed  Google Scholar 

  153. Traka M, Goutebroze L, Denisenko N, Bessa M, Nifli A, Havaki S, Iwakura Y, Fukamauchi F, Watanabe K, Soliven B, Girault JA, Karagogeos D (2003) Association of TAG-1 with Caspr2 is essential for the molecular organization of juxtaparanodal regions of myelinated fibers. J Cell Biol 162(6):1161–1172. doi:10.1083/jcb.200305078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Poliak S, Salomon D, Elhanany H, Sabanay H, Kiernan B, Pevny L, Stewart CL, Xu X, Chiu SY, Shrager P, Furley AJ, Peles E (2003) Juxtaparanodal clustering of Shaker-like K+ channels in myelinated axons depends on Caspr2 and TAG-1. J Cell Biol 162(6):1149–1160. doi:10.1083/jcb.200305018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Denisenko-Nehrbass N, Oguievetskaia K, Goutebroze L, Galvez T, Yamakawa H, Ohara O, Carnaud M, Girault JA (2003) Protein 4.1B associates with both Caspr/paranodin and Caspr2 at paranodes and juxtaparanodes of myelinated fibres. Eur J Neurosci 17(2):411–416

    Article  PubMed  Google Scholar 

  156. Strauss KA, Puffenberger EG, Huentelman MJ, Gottlieb S, Dobrin SE, Parod JM, Stephan DA, Morton DH (2006) Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2. N Engl J Med 354(13):1370–1377. doi:10.1056/NEJMoa052773

    Article  CAS  PubMed  Google Scholar 

  157. Alarcon M, Abrahams BS, Stone JL, Duvall JA, Perederiy JV, Bomar JM, Sebat J, Wigler M, Martin CL, Ledbetter DH, Nelson SF, Cantor RM, Geschwind DH (2008) Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene. Am J Hum Genet 82(1):150–159. doi:10.1016/j.ajhg.2007.09.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Arking DE, Cutler DJ, Brune CW, Teslovich TM, West K, Ikeda M, Rea A, Guy M, Lin S, Cook EH, Chakravarti A (2008) A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism. Am J Hum Genet 82(1):160–164. doi:10.1016/j.ajhg.2007.09.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Bakkaloglu B, O’Roak BJ, Louvi A, Gupta AR, Abelson JF, Morgan TM, Chawarska K, Klin A, Ercan-Sencicek AG, Stillman AA, Tanriover G, Abrahams BS, Duvall JA, Robbins EM, Geschwind DH, Biederer T, Gunel M, Lifton RP, State MW (2008) Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders. Am J Hum Genet 82(1):165–173. doi:10.1016/j.ajhg.2007.09.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Friedman JI, Vrijenhoek T, Markx S, Janssen IM, van der Vliet WA, Faas BH, Knoers NV, Cahn W, Kahn RS, Edelmann L, Davis KL, Silverman JM, Brunner HG, van Kessel AG, Wijmenga C, Ophoff RA, Veltman JA (2008) CNTNAP2 gene dosage variation is associated with schizophrenia and epilepsy. Mol Psychiatry 13(3):261–266. doi:10.1038/sj.mp.4002049

    Article  CAS  PubMed  Google Scholar 

  161. Wang KS, Liu XF, Aragam N (2010) A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder. Schizophr Res 124(1–3):192–199. doi:10.1016/j.schres.2010.09.002

    Article  PubMed  Google Scholar 

  162. Ji W, Li T, Pan Y, Tao H, Ju K, Wen Z, Fu Y, An Z, Zhao Q, Wang T, He L, Feng G, Yi Q, Shi Y (2013) CNTNAP2 is significantly associated with schizophrenia and major depression in the Han Chinese population. Psychiatry Res 207(3):225–228. doi:10.1016/j.psychres.2012.09.024

    Article  CAS  PubMed  Google Scholar 

  163. Toma C, Hervas A, Torrico B, Balmana N, Salgado M, Maristany M, Vilella E, Martinez-Leal R, Planelles MI, Cusco I, del Campo M, Perez-Jurado LA, Caballero-Andaluz R, de Diego-Otero Y, Perez-Costillas L, Ramos-Quiroga JA, Ribases M, Bayes M, Cormand B (2013) Analysis of two language-related genes in autism: a case–control association study of FOXP2 and CNTNAP2. Psychiatr Genet 23(2):82–85. doi:10.1097/YPG.0b013e32835d6fc6

    Article  CAS  PubMed  Google Scholar 

  164. Murdoch JD, Gupta AR, Sanders SJ, Walker MF, Keaney J, Fernandez TV, Murtha MT, Anyanwu S, Ober GT, Raubeson MJ, DiLullo NM, Villa N, Waqar Z, Sullivan C, Gonzalez L, Willsey AJ, Choe SY, Neale BM, Daly MJ, State MW (2015) No evidence for association of autism with rare heterozygous point mutations in contactin-associated protein-like 2 (CNTNAP2), or in other contactin-associated proteins or contactins. PLoS Genet 11(1):e1004852. doi:10.1371/journal.pgen.1004852

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  165. Truong DT, Rendall AR, Castelluccio BC, Eigsti IM, Fitch RH (2015) Auditory processing and morphological anomalies in medial geniculate nucleus of Cntnap2 mutant mice. Behav Neurosci 129(6):731–743. doi:10.1037/bne0000096

    Article  PubMed  Google Scholar 

  166. Rendall AR, Truong DT, Fitch RH (2016) Learning delays in a mouse model of autism spectrum disorder. Behav Brain Res 303:201–207. doi:10.1016/j.bbr.2016.02.006

    Article  PubMed  PubMed Central  Google Scholar 

  167. Balczon R, Bao L, Zimmer WE (1994) PCM-1, A 228-kD centrosome autoantigen with a distinct cell cycle distribution. J Cell Biol 124(5):783–793

    Article  CAS  PubMed  Google Scholar 

  168. Dammermann A, Merdes A (2002) Assembly of centrosomal proteins and microtubule organization depends on PCM-1. J Cell Biol 159(2):255–266. doi:10.1083/jcb.200204023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Kubo A, Tsukita S (2003) Non-membranous granular organelle consisting of PCM-1: subcellular distribution and cell-cycle-dependent assembly/disassembly. J Cell Sci 116(Pt 5):919–928

    Article  CAS  PubMed  Google Scholar 

  170. Kamiya A, Tan PL, Kubo K, Engelhard C, Ishizuka K, Kubo A, Tsukita S, Pulver AE, Nakajima K, Cascella NG, Katsanis N, Sawa A (2008) Recruitment of PCM1 to the centrosome by the cooperative action of DISC1 and BBS4: a candidate for psychiatric illnesses. Arch Gen Psychiatry 65(9):996–1006. doi:10.1001/archpsyc.65.9.996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. de Anda FC, Meletis K, Ge X, Rei D, Tsai LH (2010) Centrosome motility is essential for initial axon formation in the neocortex. J Neurosci 30(31):10391–10406. doi:10.1523/JNEUROSCI.0381-10.2010

    Article  PubMed  CAS  Google Scholar 

  172. Zoubovsky S, Oh EC, Cash-Padgett T, Johnson AW, Hou Z, Mori S, Gallagher M, Katsanis N, Sawa A, Jaaro-Peled H (2015) Neuroanatomical and behavioral deficits in mice haploinsufficient for Pericentriolar material 1 (Pcm1). Neurosci Res 98:45–49. doi:10.1016/j.neures.2015.02.002

    Article  PubMed  PubMed Central  Google Scholar 

  173. Eastwood SL, Hodgkinson CA, Harrison PJ (2009) DISC-1 Leu607Phe alleles differentially affect centrosomal PCM1 localization and neurotransmitter release. Mol Psychiatry 14(6):556–557. doi:10.1038/mp.2009.13

    Article  CAS  PubMed  Google Scholar 

  174. Eastwood SL, Walker M, Hyde TM, Kleinman JE, Harrison PJ (2010) The DISC1 Ser704Cys substitution affects centrosomal localization of its binding partner PCM1 in glia in human brain. Hum Mol Genet 19(12):2487–2496. doi:10.1093/hmg/ddq130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Gurling HM, Critchley H, Datta SR, McQuillin A, Blaveri E, Thirumalai S, Pimm J, Krasucki R, Kalsi G, Quested D, Lawrence J, Bass N, Choudhury K, Puri V, O’Daly O, Curtis D, Blackwood D, Muir W, Malhotra AK, Buchanan RW, Good CD, Frackowiak RS, Dolan RJ (2006) Genetic association and brain morphology studies and the chromosome 8p22 pericentriolar material 1 (PCM1) gene in susceptibility to schizophrenia. Arch Gen Psychiatry 63(8):844–854. doi:10.1001/archpsyc.63.8.844

    Article  PubMed  PubMed Central  Google Scholar 

  176. Datta SR, McQuillin A, Rizig M, Blaveri E, Thirumalai S, Kalsi G, Lawrence J, Bass NJ, Puri V, Choudhury K, Pimm J, Crombie C, Fraser G, Walker N, Curtis D, Zvelebil M, Pereira A, Kandaswamy R, St Clair D, Gurling HM (2010) A threonine to isoleucine missense mutation in the pericentriolar material 1 gene is strongly associated with schizophrenia. Mol Psychiatry 15(6):615–628. doi:10.1038/mp.2008.128

    Article  CAS  PubMed  Google Scholar 

  177. Hashimoto R, Ohi K, Yasuda Y, Fukumoto M, Yamamori H, Kamino K, Morihara T, Iwase M, Kazui H, Numata S, Ikeda M, Ueno S, Ohmori T, Iwata N, Ozaki N, Takeda M (2011) No association between the PCM1 gene and schizophrenia: a multi-center case–control study and a meta-analysis. Schizophr Res 129(1):80–84. doi:10.1016/j.schres.2011.03.024

    Article  PubMed  Google Scholar 

  178. Sakamoto S, Takaki M, Okahisa Y, Mizuki Y, Kodama M, Ujike H, Uchitomi Y (2014) Four polymorphisms of the pericentriolar material 1 (PCM1) gene are not associated with schizophrenia in a Japanese population. Psychiatry Res 216(2):288–289. doi:10.1016/j.psychres.2014.02.006

    Article  CAS  PubMed  Google Scholar 

  179. Kenedy AA, Cohen KJ, Loveys DA, Kato GJ, Dang CV (2003) Identification and characterization of the novel centrosome-associated protein CCCAP. Gene 303:35–46

    Article  CAS  PubMed  Google Scholar 

  180. Otto EA, Hurd TW, Airik R, Chaki M, Zhou W, Stoetzel C, Patil SB, Levy S, Ghosh AK, Murga-Zamalloa CA, van Reeuwijk J, Letteboer SJ, Sang L, Giles RH, Liu Q, Coene KL, Estrada-Cuzcano A, Collin RW, McLaughlin HM, Held S, Kasanuki JM, Ramaswami G, Conte J, Lopez I, Washburn J, Macdonald J, Hu J, Yamashita Y, Maher ER, Guay-Woodford LM, Neumann HP, Obermuller N, Koenekoop RK, Bergmann C, Bei X, Lewis RA, Katsanis N, Lopes V, Williams DS, Lyons RH, Dang CV, Brito DA, Dias MB, Zhang X, Cavalcoli JD, Nurnberg G, Nurnberg P, Pierce EA, Jackson PK, Antignac C, Saunier S, Roepman R, Dollfus H, Khanna H, Hildebrandt F (2010) Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy. Nat Genet 42(10):840–850. doi:10.1038/ng.662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Schaefer E, Zaloszyc A, Lauer J, Durand M, Stutzmann F, Perdomo-Trujillo Y, Redin C, Bennouna Greene V, Toutain A, Perrin L, Gerard M, Caillard S, Bei X, Lewis RA, Christmann D, Letsch J, Kribs M, Mutter C, Muller J, Stoetzel C, Fischbach M, Marion V, Katsanis N, Dollfus H (2011) Mutations in SDCCAG8/NPHP10 cause Bardet–Biedl syndrome and are associated with penetrant renal disease and absent polydactyly. Mol Syndromol 1(6):273–281. doi:10.1159/000331268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Hamshere ML, Walters JT, Smith R, Richards AL, Green E, Grozeva D, Jones I, Forty L, Jones L, Gordon-Smith K, Riley B, O’Neill FA, Kendler KS, Sklar P, Purcell S, Kranz J, Schizophrenia Psychiatric Genome-wide Association Study C, Wellcome Trust Case Control C, Wellcome Trust Case Control C, Morris D, Gill M, Holmans P, Craddock N, Corvin A, Owen MJ, O’Donovan MC (2013) Genome-wide significant associations in schizophrenia to ITIH3/4, CACNA1C and SDCCAG8, and extensive replication of associations reported by the Schizophrenia PGC. Mol Psychiatry 18(6):708–712. doi:10.1038/mp.2012.67

    Article  CAS  PubMed  Google Scholar 

  183. Insolera R, Shao W, Airik R, Hildebrandt F, Shi SH (2014) SDCCAG8 regulates pericentriolar material recruitment and neuronal migration in the developing cortex. Neuron 83(4):805–822. doi:10.1016/j.neuron.2014.06.029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Airik R, Schueler M, Airik M, Cho J, Ulanowicz KA, Porath JD, Hurd TW, Bekker-Jensen S, Schroder JM, Andersen JS, Hildebrandt F (2016) SDCCAG8 interacts with RAB effector proteins RABEP2 and ERC1 and Is required for hedgehog signaling. PLoS One 11(5):e0156081. doi:10.1371/journal.pone.0156081

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  185. Lang B, Zhang L, Jiang G, Hu L, Lan W, Zhao L, Hunter I, Pruski M, Song NN, Huang Y, Zhang L, St Clair D, McCaig CD, Ding YQ (2016) Control of cortex development by ULK4, a rare risk gene for mental disorders including schizophrenia. Sci Rep 6:31126. doi:10.1038/srep31126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Lang B, Pu J, Hunter I, Liu M, Martin-Granados C, Reilly TJ, Gao GD, Guan ZL, Li WD, Shi YY, He G, He L, Stefansson H, St Clair D, Blackwood DH, McCaig CD, Shen S (2014) Recurrent deletions of ULK4 in schizophrenia: a gene crucial for neuritogenesis and neuronal motility. J Cell Sci 127(Pt 3):630–640. doi:10.1242/jcs.137604

    Article  CAS  PubMed  Google Scholar 

  187. Vogel P, Read RW, Hansen GM, Payne BJ, Small D, Sands AT, Zambrowicz BP (2012) Congenital hydrocephalus in genetically engineered mice. Vet Pathol 49(1):166–181. doi:10.1177/0300985811415708

    Article  CAS  PubMed  Google Scholar 

  188. Liu M, Guan Z, Shen Q, Lalor P, Fitzgerald U, O’Brien T, Dockery P, Shen S (2016) Ulk4 is essential for ciliogenesis and CSF flow. J Neurosci 36(29):7589–7600. doi:10.1523/JNEUROSCI.0621-16.2016

    Article  CAS  PubMed  Google Scholar 

  189. Pilkington SJ, Walker JE (1989) Mitochondrial NADH-ubiquinone reductase: complementary DNA sequences of import precursors of the bovine and human 24-kDa subunit. Biochemistry 28(8):3257–3264

    Article  CAS  PubMed  Google Scholar 

  190. Washizuka S, Kametani M, Sasaki T, Tochigi M, Umekage T, Kohda K, Kato T (2006) Association of mitochondrial complex I subunit gene NDUFV2 at 18p11 with schizophrenia in the Japanese population. Am J Med Genet B Neuropsychiatr Genet 141B(3):301–304. doi:10.1002/ajmg.b.30285

    Article  CAS  PubMed  Google Scholar 

  191. Ben-Shachar D, Karry R (2008) Neuroanatomical pattern of mitochondrial complex I pathology varies between schizophrenia, bipolar disorder and major depression. PLoS One 3(11):e3676. doi:10.1371/journal.pone.0003676

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  192. Ayalew M, Le-Niculescu H, Levey DF, Jain N, Changala B, Patel SD, Winiger E, Breier A, Shekhar A, Amdur R, Koller D, Nurnberger JI, Corvin A, Geyer M, Tsuang MT, Salomon D, Schork NJ, Fanous AH, O’Donovan MC, Niculescu AB (2012) Convergent functional genomics of schizophrenia: from comprehensive understanding to genetic risk prediction. Mol Psychiatry 17(9):887–905. doi:10.1038/mp.2012.37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Focking M, Dicker P, Lopez LM, Hryniewiecka M, Wynne K, English JA, Cagney G, Cotter DR (2016) Proteomic analysis of the postsynaptic density implicates synaptic function and energy pathways in bipolar disorder. Transl Psychiatry 6(11):e959. doi:10.1038/tp.2016.224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Jaffrey SR, Snowman AM, Eliasson MJ, Cohen NA, Snyder SH (1998) CAPON: a protein associated with neuronal nitric oxide synthase that regulates its interactions with PSD95. Neuron 20(1):115–124

    Article  CAS  PubMed  Google Scholar 

  195. Hernandez K, Swiatkowski P, Patel MV, Liang C, Dudzinski NR, Brzustowicz LM, Firestein BL (2016) Overexpression of isoforms of nitric oxide synthase 1 adaptor protein, encoded by a risk gene for schizophrenia, alters actin dynamics and synaptic function. Front Cell Neurosci 10:6. doi:10.3389/fncel.2016.00006

    Article  PubMed  PubMed Central  Google Scholar 

  196. Carrel D, Hernandez K, Kwon M, Mau C, Trivedi MP, Brzustowicz LM, Firestein BL (2015) Nitric oxide synthase 1 adaptor protein, a protein implicated in schizophrenia, controls radial migration of cortical neurons. Biol Psychiatry 77(11):969–978. doi:10.1016/j.biopsych.2014.10.016

    Article  CAS  PubMed  Google Scholar 

  197. Greenwood TA, Lazzeroni LC, Calkins ME, Freedman R, Green MF, Gur RE, Gur RC, Light GA, Nuechterlein KH, Olincy A, Radant AD, Seidman LJ, Siever LJ, Silverman JM, Stone WS, Sugar CA, Swerdlow NR, Tsuang DW, Tsuang MT, Turetsky BI, Braff DL (2016) Genetic assessment of additional endophenotypes from the Consortium on the Genetics of Schizophrenia Family Study. Schizophr Res 170(1):30–40. doi:10.1016/j.schres.2015.11.008

    Article  PubMed  Google Scholar 

  198. Cheah SY, Lawford BR, Young RM, Morris CP, Voisey J (2015) Association of NOS1AP variants and depression phenotypes in schizophrenia. J Affect Disord 188:263–269. doi:10.1016/j.jad.2015.08.069

    Article  CAS  PubMed  Google Scholar 

  199. Husted JA, Ahmed R, Chow EW, Brzustowicz LM, Bassett AS (2010) Childhood trauma and genetic factors in familial schizophrenia associated with the NOS1AP gene. Schizophr Res 121(1–3):187–192. doi:10.1016/j.schres.2010.05.021

    Article  PubMed  PubMed Central  Google Scholar 

  200. Wratten NS, Memoli H, Huang Y, Dulencin AM, Matteson PG, Cornacchia MA, Azaro MA, Messenger J, Hayter JE, Bassett AS, Buyske S, Millonig JH, Vieland VJ, Brzustowicz LM (2009) Identification of a schizophrenia-associated functional noncoding variant in NOS1AP. Am J Psychiatry 166(4):434–441. doi:10.1176/appi.ajp.2008.08081266

    Article  PubMed  PubMed Central  Google Scholar 

  201. Kremeyer B, Garcia J, Kymalainen H, Wratten N, Restrepo G, Palacio C, Miranda AL, Lopez C, Restrepo M, Bedoya G, Brzustowicz LM, Ospina-Duque J, Arbelaez MP, Ruiz-Linares A (2009) Evidence for a role of the NOS1AP (CAPON) gene in schizophrenia and its clinical dimensions: an association study in a South American population isolate. Hum Hered 67(3):163–173. doi:10.1159/000181154

    Article  CAS  PubMed  Google Scholar 

  202. Miranda A, Garcia J, Lopez C, Gordon D, Palacio C, Restrepo G, Ortiz J, Montoya G, Cardeno C, Calle J, Lopez M, Campo O, Bedoya G, Ruiz-Linares A, Ospina-Duque J (2006) Putative association of the carboxy-terminal PDZ ligand of neuronal nitric oxide synthase gene (CAPON) with schizophrenia in a Colombian population. Schizophr Res 82(2–3):283–285. doi:10.1016/j.schres.2005.10.018

    Article  PubMed  Google Scholar 

  203. Zheng Y, Li H, Qin W, Chen W, Duan Y, Xiao Y, Li C, Zhang J, Li X, Feng G, He L (2005) Association of the carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase gene with schizophrenia in the Chinese Han population. Biochem Biophys Res Commun 328(4):809–815. doi:10.1016/j.bbrc.2005.01.037

    Article  CAS  PubMed  Google Scholar 

  204. Brzustowicz LM, Simone J, Mohseni P, Hayter JE, Hodgkinson KA, Chow EW, Bassett AS (2004) Linkage disequilibrium mapping of schizophrenia susceptibility to the CAPON region of chromosome 1q22. Am J Hum Genet 74(5):1057–1063. doi:10.1086/420774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Chen G, Sima J, Jin M, Wang KY, Xue XJ, Zheng W, Ding YQ, Yuan XB (2008) Semaphorin-3A guides radial migration of cortical neurons during development. Nat Neurosci 11(1):36–44. doi:10.1038/nn2018

    Article  PubMed  CAS  Google Scholar 

  206. Mah S, Nelson MR, Delisi LE, Reneland RH, Markward N, James MR, Nyholt DR, Hayward N, Handoko H, Mowry B, Kammerer S, Braun A (2006) Identification of the semaphorin receptor PLXNA2 as a candidate for susceptibility to schizophrenia. Mol Psychiatry 11(5):471–478. doi:10.1038/sj.mp.4001785

    Article  CAS  PubMed  Google Scholar 

  207. Zhang R, Zhong NN, Liu XG, Yan H, Qiu C, Han Y, Wang W, Hou WK, Liu Y, Gao CG, Guo TW, Lu SM, Deng HW, Ma J (2010) Is the EFNB2 locus associated with schizophrenia? Single nucleotide polymorphisms and haplotypes analysis. Psychiatry Res 180(1):5–9. doi:10.1016/j.psychres.2010.04.037

    Article  CAS  PubMed  Google Scholar 

  208. Hu Y, Li S, Jiang H, Li MT, Zhou JW (2014) Ephrin-B2/EphA4 forward signaling is required for regulation of radial migration of cortical neurons in the mouse. Neurosci Bull 30(3):425–432. doi:10.1007/s12264-013-1404-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Hu H (1999) Chemorepulsion of neuronal migration by Slit2 in the developing mammalian forebrain. Neuron 23(4):703–711

    Article  CAS  PubMed  Google Scholar 

  210. Blockus H, Chedotal A (2014) The multifaceted roles of Slits and Robos in cortical circuits: from proliferation to axon guidance and neurological diseases. Curr Opin Neurobiol 27:82–88. doi:10.1016/j.conb.2014.03.003

    Article  CAS  PubMed  Google Scholar 

  211. Gonda Y, Andrews WD, Tabata H, Namba T, Parnavelas JG, Nakajima K, Kohsaka S, Hanashima C, Uchino S (2013) Robo1 regulates the migration and laminar distribution of upper-layer pyramidal neurons of the cerebral cortex. Cereb Cortex 23(6):1495–1508. doi:10.1093/cercor/bhs141

    Article  PubMed  Google Scholar 

  212. Zheng W, Geng AQ, Li PF, Wang Y, Yuan XB (2012) Robo4 regulates the radial migration of newborn neurons in developing neocortex. Cereb Cortex 22(11):2587–2601. doi:10.1093/cercor/bhr330

    Article  PubMed  Google Scholar 

  213. Anitha A, Nakamura K, Yamada K, Suda S, Thanseem I, Tsujii M, Iwayama Y, Hattori E, Toyota T, Miyachi T, Iwata Y, Suzuki K, Matsuzaki H, Kawai M, Sekine Y, Tsuchiya K, Sugihara G, Ouchi Y, Sugiyama T, Koizumi K, Higashida H, Takei N, Yoshikawa T, Mori N (2008) Genetic analyses of roundabout (ROBO) axon guidance receptors in autism. Am J Med Genet B Neuropsychiatr Genet 147B(7):1019–1027. doi:10.1002/ajmg.b.30697

    Article  CAS  PubMed  Google Scholar 

  214. Millar JK, Wilson-Annan JC, Anderson S, Christie S, Taylor MS, Semple CA, Devon RS, St Clair DM, Muir WJ, Blackwood DH, Porteous DJ (2000) Disruption of two novel genes by a translocation co-segregating with schizophrenia. Hum Mol Genet 9(9):1415–1423

    Article  CAS  PubMed  Google Scholar 

  215. Morris JA, Kandpal G, Ma L, Austin CP (2003) DISC1 (disrupted-in-schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation. Hum Mol Genet 12(13):1591–1608

    Article  CAS  PubMed  Google Scholar 

  216. Miyoshi K, Asanuma M, Miyazaki I, Diaz-Corrales FJ, Katayama T, Tohyama M, Ogawa N (2004) DISC1 localizes to the centrosome by binding to kendrin. Biochem Biophys Res Commun 317(4):1195–1199. doi:10.1016/j.bbrc.2004.03.163

    Article  CAS  PubMed  Google Scholar 

  217. Shimizu S, Matsuzaki S, Hattori T, Kumamoto N, Miyoshi K, Katayama T, Tohyama M (2008) DISC1-kendrin interaction is involved in centrosomal microtubule network formation. Biochem Biophys Res Commun 377(4):1051–1056. doi:10.1016/j.bbrc.2008.10.100

    Article  CAS  PubMed  Google Scholar 

  218. Bradshaw NJ, Ogawa F, Antolin-Fontes B, Chubb JE, Carlyle BC, Christie S, Claessens A, Porteous DJ, Millar JK (2008) DISC1, PDE4B, and NDE1 at the centrosome and synapse. Biochem Biophys Res Commun 377(4):1091–1096. doi:10.1016/j.bbrc.2008.10.120

    Article  CAS  PubMed  Google Scholar 

  219. Bradshaw NJ, Soares DC, Carlyle BC, Ogawa F, Davidson-Smith H, Christie S, Mackie S, Thomson PA, Porteous DJ, Millar JK (2011) PKA phosphorylation of NDE1 is DISC1/PDE4 dependent and modulates its interaction with LIS1 and NDEL1. J Neurosci 31(24):9043–9054. doi:10.1523/JNEUROSCI.5410-10.2011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  220. Kamiya A, Kubo K, Tomoda T, Takaki M, Youn R, Ozeki Y, Sawamura N, Park U, Kudo C, Okawa M, Ross CA, Hatten ME, Nakajima K, Sawa A (2005) A schizophrenia-associated mutation of DISC1 perturbs cerebral cortex development. Nat Cell Biol 7(12):1167–1178. doi:10.1038/ncb1328

    Article  PubMed  CAS  Google Scholar 

  221. Enomoto A, Murakami H, Asai N, Morone N, Watanabe T, Kawai K, Murakumo Y, Usukura J, Kaibuchi K, Takahashi M (2005) Akt/PKB regulates actin organization and cell motility via Girdin/APE. Dev Cell 9(3):389–402. doi:10.1016/j.devcel.2005.08.001

    Article  CAS  PubMed  Google Scholar 

  222. Enomoto A, Asai N, Namba T, Wang Y, Kato T, Tanaka M, Tatsumi H, Taya S, Tsuboi D, Kuroda K, Kaneko N, Sawamoto K, Miyamoto R, Jijiwa M, Murakumo Y, Sokabe M, Seki T, Kaibuchi K, Takahashi M (2009) Roles of disrupted-in-schizophrenia 1-interacting protein girdin in postnatal development of the dentate gyrus. Neuron 63(6):774–787. doi:10.1016/j.neuron.2009.08.015

    Article  CAS  PubMed  Google Scholar 

  223. Nechipurenko IV, Olivier-Mason A, Kazatskaya A, Kennedy J, McLachlan IG, Heiman MG, Blacque OE, Sengupta P (2016) A conserved role for girdin in basal body positioning and ciliogenesis. Dev Cell 38(5):493–506. doi:10.1016/j.devcel.2016.07.013

    Article  CAS  PubMed  Google Scholar 

  224. Koike H, Arguello PA, Kvajo M, Karayiorgou M, Gogos JA (2006) Disc1 is mutated in the 129S6/SvEv strain and modulates working memory in mice. Proc Natl Acad Sci USA 103(10):3693–3697. doi:10.1073/pnas.0511189103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Hikida T, Jaaro-Peled H, Seshadri S, Oishi K, Hookway C, Kong S, Wu D, Xue R, Andrade M, Tankou S, Mori S, Gallagher M, Ishizuka K, Pletnikov M, Kida S, Sawa A (2007) Dominant-negative DISC1 transgenic mice display schizophrenia-associated phenotypes detected by measures translatable to humans. Proc Natl Acad Sci USA 104(36):14501–14506. doi:10.1073/pnas.0704774104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  226. Li W, Zhou Y, Jentsch JD, Brown RA, Tian X, Ehninger D, Hennah W, Peltonen L, Lonnqvist J, Huttunen MO, Kaprio J, Trachtenberg JT, Silva AJ, Cannon TD (2007) Specific developmental disruption of disrupted-in-schizophrenia-1 function results in schizophrenia-related phenotypes in mice. Proc Natl Acad Sci USA 104(46):18280–18285. doi:10.1073/pnas.0706900104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  227. Pletnikov MV, Ayhan Y, Xu Y, Nikolskaia O, Ovanesov M, Huang H, Mori S, Moran TH, Ross CA (2008) Enlargement of the lateral ventricles in mutant DISC1 transgenic mice. Mol Psychiatry 13(2):115. doi:10.1038/sj.mp.4002144

    Article  CAS  PubMed  Google Scholar 

  228. Ayhan Y, Abazyan B, Nomura J, Kim R, Ladenheim B, Krasnova IN, Sawa A, Margolis RL, Cadet JL, Mori S, Vogel MW, Ross CA, Pletnikov MV (2011) Differential effects of prenatal and postnatal expressions of mutant human DISC1 on neurobehavioral phenotypes in transgenic mice: evidence for neurodevelopmental origin of major psychiatric disorders. Mol Psychiatry 16(3):293–306. doi:10.1038/mp.2009.144

    Article  CAS  PubMed  Google Scholar 

  229. Niwa M, Kamiya A, Murai R, Kubo K, Gruber AJ, Tomita K, Lu L, Tomisato S, Jaaro-Peled H, Seshadri S, Hiyama H, Huang B, Kohda K, Noda Y, O’Donnell P, Nakajima K, Sawa A, Nabeshima T (2010) Knockdown of DISC1 by in utero gene transfer disturbs postnatal dopaminergic maturation in the frontal cortex and leads to adult behavioral deficits. Neuron 65(4):480–489. doi:10.1016/j.neuron.2010.01.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  230. Kvajo M, McKellar H, Arguello PA, Drew LJ, Moore H, MacDermott AB, Karayiorgou M, Gogos JA (2008) A mutation in mouse Disc1 that models a schizophrenia risk allele leads to specific alterations in neuronal architecture and cognition. Proc Natl Acad Sci USA 105(19):7076–7081. doi:10.1073/pnas.0802615105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  231. Johnson AW, Jaaro-Peled H, Shahani N, Sedlak TW, Zoubovsky S, Burruss D, Emiliani F, Sawa A, Gallagher M (2013) Cognitive and motivational deficits together with prefrontal oxidative stress in a mouse model for neuropsychiatric illness. Proc Natl Acad Sci USA 110(30):12462–12467. doi:10.1073/pnas.1307925110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  232. Clapcote SJ, Lipina TV, Millar JK, Mackie S, Christie S, Ogawa F, Lerch JP, Trimble K, Uchiyama M, Sakuraba Y, Kaneda H, Shiroishi T, Houslay MD, Henkelman RM, Sled JG, Gondo Y, Porteous DJ, Roder JC (2007) Behavioral phenotypes of Disc1 missense mutations in mice. Neuron 54(3):387–402. doi:10.1016/j.neuron.2007.04.015

    Article  CAS  PubMed  Google Scholar 

  233. Lipina TV, Niwa M, Jaaro-Peled H, Fletcher PJ, Seeman P, Sawa A, Roder JC (2010) Enhanced dopamine function in DISC1-L100P mutant mice: implications for schizophrenia. Genes Brain Behav 9(7):777–789. doi:10.1111/j.1601-183X.2010.00615.x

    Article  CAS  PubMed  Google Scholar 

  234. Kuroda K, Yamada S, Tanaka M, Iizuka M, Yano H, Mori D, Tsuboi D, Nishioka T, Namba T, Iizuka Y, Kubota S, Nagai T, Ibi D, Wang R, Enomoto A, Isotani-Sakakibara M, Asai N, Kimura K, Kiyonari H, Abe T, Mizoguchi A, Sokabe M, Takahashi M, Yamada K, Kaibuchi K (2011) Behavioral alterations associated with targeted disruption of exons 2 and 3 of the Disc1 gene in the mouse. Hum Mol Genet 20(23):4666–4683. doi:10.1093/hmg/ddr400

    Article  CAS  PubMed  Google Scholar 

  235. Hennah W, Varilo T, Kestila M, Paunio T, Arajarvi R, Haukka J, Parker A, Martin R, Levitzky S, Partonen T, Meyer J, Lonnqvist J, Peltonen L, Ekelund J (2003) Haplotype transmission analysis provides evidence of association for DISC1 to schizophrenia and suggests sex-dependent effects. Hum Mol Genet 12(23):3151–3159. doi:10.1093/hmg/ddg341

    Article  CAS  PubMed  Google Scholar 

  236. Callicott JH, Straub RE, Pezawas L, Egan MF, Mattay VS, Hariri AR, Verchinski BA, Meyer-Lindenberg A, Balkissoon R, Kolachana B, Goldberg TE, Weinberger DR (2005) Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia. Proc Natl Acad Sci USA 102(24):8627–8632. doi:10.1073/pnas.0500515102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  237. Hennah W, Tomppo L, Hiekkalinna T, Palo OM, Kilpinen H, Ekelund J, Tuulio-Henriksson A, Silander K, Partonen T, Paunio T, Terwilliger JD, Lonnqvist J, Peltonen L (2007) Families with the risk allele of DISC1 reveal a link between schizophrenia and another component of the same molecular pathway, NDE1. Hum Mol Genet 16(5):453–462. doi:10.1093/hmg/ddl462

    Article  CAS  PubMed  Google Scholar 

  238. Schumacher J, Laje G, Abou Jamra R, Becker T, Muhleisen TW, Vasilescu C, Mattheisen M, Herms S, Hoffmann P, Hillmer AM, Georgi A, Herold C, Schulze TG, Propping P, Rietschel M, McMahon FJ, Nothen MM, Cichon S (2009) The DISC locus and schizophrenia: evidence from an association study in a central European sample and from a meta-analysis across different European populations. Hum Mol Genet 18(14):2719–2727. doi:10.1093/hmg/ddp204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  239. Kilpinen H, Ylisaukko-Oja T, Hennah W, Palo OM, Varilo T, Vanhala R, Nieminen-von Wendt T, von Wendt L, Paunio T, Peltonen L (2008) Association of DISC1 with autism and Asperger syndrome. Mol Psychiatry 13(2):187–196. doi:10.1038/sj.mp.4002031

    Article  CAS  PubMed  Google Scholar 

  240. Carless MA, Glahn DC, Johnson MP, Curran JE, Bozaoglu K, Dyer TD, Winkler AM, Cole SA, Almasy L, MacCluer JW, Duggirala R, Moses EK, Goring HH, Blangero J (2011) Impact of DISC1 variation on neuroanatomical and neurocognitive phenotypes. Mol Psychiatry 16(11):1096–1104, 1063. doi:10.1038/mp.2011.37

  241. Thomson PA, Parla JS, McRae AF, Kramer M, Ramakrishnan K, Yao J, Soares DC, McCarthy S, Morris SW, Cardone L, Cass S, Ghiban E, Hennah W, Evans KL, Rebolini D, Millar JK, Harris SE, Starr JM, MacIntyre DJ, Generation S, McIntosh AM, Watson JD, Deary IJ, Visscher PM, Blackwood DH, McCombie WR, Porteous DJ (2014) 708 common and 2010 rare DISC1 locus variants identified in 1542 subjects: analysis for association with psychiatric disorder and cognitive traits. Mol Psychiatry 19(6):668–675. doi:10.1038/mp.2013.68

    Article  CAS  PubMed  Google Scholar 

  242. Kanduri C, Kantojarvi K, Salo PM, Vanhala R, Buck G, Blancher C, Lahdesmaki H, Jarvela I (2016) The landscape of copy number variations in Finnish families with autism spectrum disorders. Autism Res 9(1):9–16. doi:10.1002/aur.1502

    Article  PubMed  Google Scholar 

  243. Mathieson I, Munafo MR, Flint J (2012) Meta-analysis indicates that common variants at the DISC1 locus are not associated with schizophrenia. Mol Psychiatry 17(6):634–641. doi:10.1038/mp.2011.41

    Article  CAS  PubMed  Google Scholar 

  244. Schizophrenia Working Group of the Psychiatric Genomics C (2014) Biological insights from 108 schizophrenia-associated genetic loci. Nature 511(7510):421–427. doi:10.1038/nature13595

    Article  CAS  Google Scholar 

  245. Sullivan PF (2013) Questions about DISC1 as a genetic risk factor for schizophrenia. Mol Psychiatry 18(10):1050–1052. doi:10.1038/mp.2012.182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  246. Fukuda T, Sugita S, Inatome R, Yanagi S (2010) CAMDI, a novel disrupted in Schizophrenia 1 (DISC1)-binding protein, is required for radial migration. J Biol Chem 285(52):40554–40561. doi:10.1074/jbc.M110.179481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  247. Fukuda T, Nagashima S, Abe T, Kiyonari H, Inatome R, Yanagi S (2016) Rescue of CAMDI deletion-induced delayed radial migration and psychiatric behaviors by HDAC6 inhibitor. EMBO Rep 17(12):1785–1798. doi:10.15252/embr.201642416

    Article  CAS  PubMed  Google Scholar 

  248. Just MA, Cherkassky VL, Keller TA, Kana RK, Minshew NJ (2007) Functional and anatomical cortical underconnectivity in autism: evidence from an FMRI study of an executive function task and corpus callosum morphometry. Cereb Cortex 17(4):951–961. doi:10.1093/cercor/bhl006

    Article  PubMed  Google Scholar 

  249. Frazier TW, Keshavan MS, Minshew NJ, Hardan AY (2012) A two-year longitudinal MRI study of the corpus callosum in autism. J Autism Dev Disord 42(11):2312–2322. doi:10.1007/s10803-012-1478-z

    Article  PubMed  PubMed Central  Google Scholar 

  250. Courchesne E, Pierce K (2005) Why the frontal cortex in autism might be talking only to itself: local over-connectivity but long-distance disconnection. Curr Opin Neurobiol 15(2):225–230. doi:10.1016/j.conb.2005.03.001

    Article  CAS  PubMed  Google Scholar 

  251. Geschwind DH, Levitt P (2007) Autism spectrum disorders: developmental disconnection syndromes. Curr Opin Neurobiol 17(1):103–111. doi:10.1016/j.conb.2007.01.009

    Article  CAS  PubMed  Google Scholar 

  252. Pugacheva EN, Jablonski SA, Hartman TR, Henske EP, Golemis EA (2007) HEF1-dependent Aurora A activation induces disassembly of the primary cilium. Cell 129(7):1351–1363. doi:10.1016/j.cell.2007.04.035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  253. Kim AH, Puram SV, Bilimoria PM, Ikeuchi Y, Keough S, Wong M, Rowitch D, Bonni A (2009) A centrosomal Cdc20-APC pathway controls dendrite morphogenesis in postmitotic neurons. Cell 136(2):322–336. doi:10.1016/j.cell.2008.11.050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  254. Sanchez de Diego A, Alonso Guerrero A, Martinez AC, van Wely KH (2014) Dido3-dependent HDAC6 targeting controls cilium size. Nat Commun 5:3500. doi:10.1038/ncomms4500

    PubMed  Google Scholar 

  255. Ran J, Yang Y, Li D, Liu M, Zhou J (2015) Deacetylation of alpha-tubulin and cortactin is required for HDAC6 to trigger ciliary disassembly. Sci Rep 5:12917. doi:10.1038/srep12917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  256. Butler KV, Kalin J, Brochier C, Vistoli G, Langley B, Kozikowski AP (2010) Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, Tubastatin A. J Am Chem Soc 132(31):10842–10846. doi:10.1021/ja102758v

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  257. Yan Z, Kim E, Datta D, Lewis DA, Soderling SH (2016) Synaptic actin dysregulation, a convergent mechanism of mental disorders? J Neurosci 36(45):11411–11417. doi:10.1523/JNEUROSCI.2360-16.2016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  258. Marchisella F, Coffey ET, Hollos P (2016) Microtubule and microtubule associated protein anomalies in psychiatric disease. Cytoskeleton (Hoboken) 73(10):596–611. doi:10.1002/cm.21300

    Article  CAS  Google Scholar 

  259. Wong GT, Chang RC, Law AC (2013) A breach in the scaffold: the possible role of cytoskeleton dysfunction in the pathogenesis of major depression. Ageing Res Rev 12(1):67–75. doi:10.1016/j.arr.2012.08.004

    Article  CAS  PubMed  Google Scholar 

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  1. Laboratory of Molecular Biochemistry, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan

    Toshifumi Fukuda & Shigeru Yanagi

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  1. Toshifumi Fukuda
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  2. Shigeru Yanagi
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Correspondence to Toshifumi Fukuda or Shigeru Yanagi.

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Fukuda, T., Yanagi, S. Psychiatric behaviors associated with cytoskeletal defects in radial neuronal migration. Cell. Mol. Life Sci. 74, 3533–3552 (2017). https://doi.org/10.1007/s00018-017-2539-4

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