Skip to main content
SpringerLink
Log in

Developmentally Regulated Ca2+-Dependent Activator Protein for Secretion 2 (CAPS2) is Involved in BDNF Secretion and is Associated with Autism Susceptibility

  • Published:
The Cerebellum Aims and scope Submit manuscript

Abstract

The postnatal development of the cerebellum is accomplished via a series of cytogenetic and morphogenetic events encoded in the genome. To decipher the underlying genetic basis of these events we have systematized the spatio-temporal gene expression profiles during mouse cerebellar development in the Cerebellar Development Transcriptome Database (CDT-DB). Using the CDT-DB, Ca2+-dependent activator protein for secretion 2 (CAPS2 or CADPS2) was identified as a developmentally regulated gene that is predominantly expressed in cerebellar granule cells (GCs) with an expression peak around the first or second postnatal week. CAPS2 protein is concentrated in parallel fiber (PF) terminals and is associated with secretory vesicles containing brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). CAPS2 enhances release of BDNF and NT-3, both of which are essential for normal cerebellar development. CAPS2-deficient (CAPS2−/−) mice show reduced secretion of BDNF and NT-3; consequently, the cerebella of these mice exhibit developmental deficits, such as delayed development and increased cell death in GCs, fewer branched dendrites on Purkinje cells (PCs), and loss of the intercrural fissure. The PF-PC synapses have aberrant cytoarchitectures and electrophysiological properties. These abnormal cellular and morphological phenotypes are more severe around the cerebellar vermis, in which hypoplasia has been reported in autism patients. Moreover, CAPS2−/− mice had fewer cortical and hippocampal parvalbumin-positive interneurons and some autistic-like behavioral phenotypes. In the CAPS2 genes of some autistic patients an aberrant splicing variant and non-synonymous SNPs have been identified. These recent studies implicate CAPS2 in autism susceptibility. Therefore, CAPS2−/− mice will be a useful model animal in which to study aspects of the neuropathology and behaviors characteristic of developmental disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.

Similar content being viewed by others

References

  1. Sato A, Sekine Y, Saruta C, Nishibe H, Morita N, Sato Y, Sadakata T, Shinoda Y, Kojima T, Furuichi T (2008) Cerebellar development transcriptome database (CDT-DB): profiling of spatio-temporal gene expression during the postnatal development of mouse cerebellum. Neural Netw 21:1056–1069

    Article  PubMed  Google Scholar 

  2. Sadakata T, Furuichi T (2006) Identification and mRNA expression of Ogdh, QP-C, and two predicted genes in the postnatal mouse brain. Neurosci Lett 405:217–222

    Article  PubMed  CAS  Google Scholar 

  3. Sadakata T, Mizoguchi A, Sato Y, Katoh-Semba R, Fukuda M, Mikoshiba K, Furuichi T (2004) The secretory granule-associated protein CAPS2 regulates neurotrophin release and cell survival. J Neurosci 24:43–52

    Article  PubMed  CAS  Google Scholar 

  4. Sadakata T, Washida M, Furuichi T (2007) Alternative splicing variations in mouse CAPS2: differential expression and functional properties of splicing variants. BMC Neurosci 8:25

    Article  PubMed  CAS  Google Scholar 

  5. Sadakata T, Kakegawa W, Mizoguchi A, Washida M, Katoh-Semba R, Shutoh F, Okamoto T, Nakashima H, Kimura K, Tanaka M, Sekine Y, Itohara S, Yuzaki M, Nagao S, Furuichi T (2007) Impaired cerebellar development and function in mice lacking CAPS2, a protein involved in neurotrophin release. J Neurosci 27:2472–2482

    Article  PubMed  CAS  Google Scholar 

  6. Sadakata T, Washida M, Iwayama Y, Shoji S, Sato Y, Ohkura T, Katoh-Semba R, Nakajima M, Sekine Y, Tanaka M, Nakamura K, Iwata Y, Tsuchiya KJ, Mori N, Detera-Wadleigh SD, Ichikawa H, Itohara S, Yoshikawa T, Furuichi T (2007) Autistic-like phenotypes in Cadps2-knockout mice and aberrant CADPS2 splicing in autistic patients. J Clin Invest 117:931–943

    Article  PubMed  CAS  Google Scholar 

  7. Sadakata T, Itakura M, Kozaki S, Sekine Y, Takahashi M, Furuichi T (2006) Differential distributions of the Ca2+-dependent activator protein for secretion family proteins (CAPS2 and CAPS1) in the mouse brain. J Comp Neurol 495:735–753

    Article  PubMed  CAS  Google Scholar 

  8. Shiraishi-Yamaguchi Y, Furuichi T (2007) The Homer family proteins. Genome Biol 8:206

    Article  PubMed  CAS  Google Scholar 

  9. Shiraishi Y, Mizutani A, Bito H, Fujisawa K, Narumiya S, Mikoshiba K, Furuichi T (1999) Cupidin, an isoform of Homer/Vesl, interacts with the actin cytoskeleton and activated rho family small GTPases and is expressed in developing mouse cerebellar granule cells. J Neurosci 19:8389–8400

    PubMed  CAS  Google Scholar 

  10. Huang J, Sakai R, Furuichi T (2006) The docking protein Cas links tyrosine phosphorylation signaling to elongation of cerebellar granule cell axons. Mol Biol Cell 17:3187–3196

    Article  PubMed  CAS  Google Scholar 

  11. Huang J, Furuya A, Furuichi T (2007) Very-KIND, a KIND domain containing RasGEF, controls dendrite growth by linking Ras small GTPases and MAP2. J Cell Biol 179:539–552

    Article  PubMed  CAS  Google Scholar 

  12. Yoshikawa F, Sato Y, Tohyama K, Akagi T, Hashikawa T, Nagakura-Takagi Y, Sekine Y, Morita N, Baba H, Suzuki Y, Sugano S, Sato A, Furuichi T (2008) Opalin, a transmembrane sialylglycoprotein located in the central nervous system myelin paranodal loop membrane. J Biol Chem 283:20830–20840

    Article  PubMed  CAS  Google Scholar 

  13. Aruga J, Yoshikawa F, Nozaki Y, Sakaki Y, Toyoda A, Furuichi T (2007) An oligodendrocyte enhancer in a phylogenetically conserved intron region of the mammalian myelin gene Opalin. J Neurochem 102:1533–1547

    Article  PubMed  CAS  Google Scholar 

  14. Speidel D, Varoqueaux F, Enk C, Nojiri M, Grishanin RN, Martin TF, Hofmann K, Brose N, Reim K (2003) A family of Ca2+-dependent activator proteins for secretion: comparative analysis of structure, expression, localization, and function. J Biol Chem 278:52802–52809

    Article  PubMed  CAS  Google Scholar 

  15. Cisternas FA, Vincent JB, Scherer SW, Ray PN (2003) Cloning and characterization of human CADPS and CADPS2, new members of the Ca2+-dependent activator for secretion protein family. Genomics 81:279–291

    Article  PubMed  CAS  Google Scholar 

  16. Berwin B, Floor E, Martin TF (1998) CAPS (mammalian UNC-31) protein localizes to membranes involved in dense-core vesicle exocytosis. Neuron 21:137–145

    Article  PubMed  CAS  Google Scholar 

  17. Tandon A, Bannykh S, Kowalchyk JA, Banerjee A, Martin TF, Balch WE (1998) Differential regulation of exocytosis by calcium and CAPS in semi-intact synaptosomes. Neuron 21:147–154

    Article  PubMed  CAS  Google Scholar 

  18. Renden R, Berwin B, Davis W, Ann K, Chin CT, Kreber R, Ganetzky B, Martin TF, Broadie K (2001) Drosophila CAPS is an essential gene that regulates dense-core vesicle release and synaptic vesicle fusion. Neuron 31:421–437

    Article  PubMed  CAS  Google Scholar 

  19. Ann K, Kowalchyk JA, Loyet KM, Martin TF (1997) Novel Ca2+-binding protein (CAPS) related to UNC-31 required for Ca2+-activated exocytosis. J Biol Chem 272:19637–19640

    Article  PubMed  CAS  Google Scholar 

  20. Elhamdani A, Martin TF, Kowalchyk JA, Artalejo CR (1999) Ca2+-dependent activator protein for secretion is critical for the fusion of dense-core vesicles with the membrane in calf adrenal chromaffin cells. J Neurosci 19:7375–7383

    PubMed  CAS  Google Scholar 

  21. Waselle L, Gerona RR, Vitale N, Martin TF, Bader MF, Regazzi R (2005) Role of phosphoinositide signaling in the control of insulin exocytosis. Mol Endocrinol 19:3097–3106

    Article  PubMed  CAS  Google Scholar 

  22. Speidel D, Salehi A, Obermueller S, Lundquist I, Brose N, Renstrom E, Rorsman P (2008) CAPS1 and CAPS2 regulate stability and recruitment of insulin granules in mouse pancreatic beta cells. Cell Metab 7:57–67

    Article  PubMed  CAS  Google Scholar 

  23. Rybkin II, Kim MS, Bezprozvannaya S, Qi X, Richardson JA, Plato CF, Hill JA, Bassel-Duby R, Olson EN (2007) Regulation of atrial natriuretic peptide secretion by a novel Ras-like protein. J Cell Biol 179:527–537

    Article  PubMed  CAS  Google Scholar 

  24. Eisenhofer G, Huynh TT, Elkahloun A, Morris JC, Bratslavsky G, Linehan WM, Zhuang Z, Balgley BM, Lee CS, Mannelli M, Lenders JW, Bornstein SR, Pacak K (2008) Differential expression of the regulated catecholamine secretory pathway in different hereditary forms of pheochromocytoma. Am J Physiol Endocrinol Metab 295:E1223–1233

    Article  PubMed  CAS  Google Scholar 

  25. Grishanin RN, Klenchin VA, Loyet KM, Kowalchyk JA, Ann K, Martin TF (2002) Membrane association domains in Ca2+-dependent activator protein for secretion mediate plasma membrane and dense-core vesicle binding required for Ca2+-dependent exocytosis. J Biol Chem 277:22025–22034

    Article  PubMed  CAS  Google Scholar 

  26. Grishanin RN, Kowalchyk JA, Klenchin VA, Ann K, Earles CA, Chapman ER, Gerona RR, Martin TF (2004) CAPS acts at a prefusion step in dense-core vesicle exocytosis as a PIP2 binding protein. Neuron 43:551–562

    Article  PubMed  CAS  Google Scholar 

  27. Osborne SL, Wallis TP, Jimenez JL, Gorman JJ, Meunier FA (2007) Identification of secretory granule phosphatidylinositol 4,5-bisphosphate-interacting proteins using an affinity pulldown strategy. Mol Cell Proteomics 6:1158–1169

    Article  PubMed  CAS  Google Scholar 

  28. James DJ, Khodthong C, Kowalchyk JA, Martin TF (2008) Phosphatidylinositol 4,5-bisphosphate regulates SNARE-dependent membrane fusion. J Cell Biol 182:355–366

    Article  PubMed  CAS  Google Scholar 

  29. Speese S, Petrie M, Schuske K, Ailion M, Ann K, Iwasaki K, Jorgensen EM, Martin TF (2007) UNC-31 (CAPS) is required for dense-core vesicle but not synaptic vesicle exocytosis in Caenorhabditis elegans. J Neurosci 27:6150–6162

    Article  PubMed  CAS  Google Scholar 

  30. Hammarlund M, Watanabe S, Schuske K, Jorgensen EM (2008) CAPS and syntaxin dock dense core vesicles to the plasma membrane in neurons. J Cell Biol 180:483–491

    Article  PubMed  CAS  Google Scholar 

  31. Speidel D, Bruederle CE, Enk C, Voets T, Varoqueaux F, Reim K, Becherer U, Fornai F, Ruggieri S, Holighaus Y, Weihe E, Bruns D, Brose N, Rettig J (2005) CAPS1 regulates catecholamine loading of large dense-core vesicles. Neuron 46:75–88

    Article  PubMed  CAS  Google Scholar 

  32. Brunk I, Blex C, Speidel D, Brose N, Ahnert-Hilger G (2008) Ca2+-dependent activator proteins of secretion promote vesicular monoamine uptake. J Biol Chem 284:1050–1056

    Article  PubMed  CAS  Google Scholar 

  33. Jockusch WJ, Speidel D, Sigler A, Sorensen JB, Varoqueaux F, Rhee JS, Brose N (2007) CAPS-1 and CAPS-2 are essential synaptic vesicle priming proteins. Cell 131:796–808

    Article  PubMed  CAS  Google Scholar 

  34. Fujita Y, Xu A, Xie L, Arunachalam L, Chou TC, Jiang T, Chiew SK, Kourtesis J, Wang L, Gaisano HY, Sugita S (2007) Ca2+-dependent activator protein for secretion 1 is critical for constitutive and regulated exocytosis but not for loading of transmitters into dense core vesicles. J Biol Chem 282:21392–21403

    Article  PubMed  CAS  Google Scholar 

  35. Zhou KM, Dong YM, Ge Q, Zhu D, Zhou W, Lin XG, Liang T, Wu ZX, Xu T (2007) PKA activation bypasses the requirement for UNC-31 in the docking of dense core vesicles from C. elegans neurons. Neuron 56:657–669

    Article  PubMed  CAS  Google Scholar 

  36. Cai T, Fukushige T, Notkins AL, Krause M (2004) Insulinoma-Associated Protein IA-2, a Vesicle Transmembrane Protein, Genetically Interacts with UNC-31/CAPS and Affects Neurosecretion in Caenorhabditis elegans. J Neurosci 24:3115–3124

    Article  PubMed  CAS  Google Scholar 

  37. Gracheva EO, Burdina AO, Touroutine D, Berthelot-Grosjean M, Parekh H, Richmond JE (2007) Tomosyn negatively regulates CAPS-dependent peptide release at Caenorhabditis elegans synapses. J Neurosci 27:10176–10184

    Article  PubMed  CAS  Google Scholar 

  38. Binda AV, Kabbani N, Levenson R (2005) Regulation of dense core vesicle release from PC12 cells by interaction between the D2 dopamine receptor and calcium-dependent activator protein for secretion (CAPS). Biochem Pharmacol 69:1451–1461

    Article  PubMed  CAS  Google Scholar 

  39. Charlie NK, Schade MA, Thomure AM, Miller KG (2006) Presynaptic UNC-31 (CAPS) is required to activate the Gαs pathway of the Caenorhabditis elegans synaptic signaling network. Genetics 172:943–961

    Article  PubMed  CAS  Google Scholar 

  40. Austin MC, Schultzberg M, Abbott LC, Montpied P, Evers JR, Paul SM, Crawley JN (1992) Expression of tyrosine hydroxylase in cerebellar Purkinje neurons of the mutant tottering and leaner mouse. Brain Res Mol Brain Res 15:227–240

    Article  PubMed  CAS  Google Scholar 

  41. Takada M, Sugimoto T, Hattori T (1993) Tyrosine hydroxylase immunoreactivity in cerebellar Purkinje cells of the rat. Neurosci Lett 150:61–64

    Article  PubMed  CAS  Google Scholar 

  42. Verney C, Grzanna R, Farkas E (1982) Distribution of dopamine-β-hydroxylase-like immunoreactive fibers in the rat cerebellar cortex during ontogeny. Dev Neurosci 5:369–374

    Article  PubMed  CAS  Google Scholar 

  43. Fernandes ML, Saad MJ, Velloso LA (2001) Effects of age on elements of insulin-signaling pathway in central nervous system of rats. Endocrine 16:227–234

    Article  PubMed  CAS  Google Scholar 

  44. de LAFML, Saad MJ, Velloso LA (1999) Insulin induces tyrosine phosphorylation of the insulin receptor and SHC, and SHC/GRB2 association in cerebellum but not in forebrain cortex of rats. Brain Res 826:74–82

    Article  Google Scholar 

  45. Sherrard RM, Bower AJ (2002) Climbing fiber development: do neurotrophins have a part to play? Cerebellum 1:265–275

    Article  PubMed  CAS  Google Scholar 

  46. Katoh-Semba R, Takeuchi IK, Semba R, Kato K (1997) Distribution of brain-derived neurotrophic factor in rats and its changes with development in the brain. J Neurochem 69:34–42

    PubMed  CAS  Google Scholar 

  47. Katoh-Semba R, Takeuchi IK, Semba R, Kato K (2000) Neurotrophin-3 controls proliferation of granular precursors as well as survival of mature granule neurons in the developing rat cerebellum. J Neurochem 74:1923–1930

    Article  PubMed  CAS  Google Scholar 

  48. Das KP, Chao SL, White LD, Haines WT, Harry GJ, Tilson HA, Barone S Jr (2001) Differential patterns of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 mRNA and protein levels in developing regions of rat brain. Neuroscience 103:739–761

    Article  PubMed  CAS  Google Scholar 

  49. Lindholm D, Hamner S, Zirrgiebel U (1997) Neurotrophins and cerebellar development. Perspect Dev Neurobiol 5:83–94

    PubMed  CAS  Google Scholar 

  50. Lindholm D, Castren E, Tsoulfas P, Kolbeck R, Berzaghi Mda P, Leingartner A, Heisenberg CP, Tessarollo L, Parada LF, Thoenen H (1993) Neurotrophin-3 induced by tri-iodothyronine in cerebellar granule cells promotes Purkinje cell differentiation. J Cell Biol 122:443–450

    Article  PubMed  CAS  Google Scholar 

  51. Segal RA, Pomeroy SL, Stiles CD (1995) Axonal growth and fasciculation linked to differential expression of BDNF and NT3 receptors in developing cerebellar granule cells. J Neurosci 15:4970–4981

    PubMed  CAS  Google Scholar 

  52. Gao WQ, Zheng JL, Karihaloo M (1995) Neurotrophin-4/5 (NT-4/5) and brain-derived neurotrophic factor (BDNF) act at later stages of cerebellar granule cell differentiation. J Neurosci 15:2656–2667

    PubMed  CAS  Google Scholar 

  53. Larkfors L, Lindsay RM, Alderson RF (1996) Characterization of the responses of Purkinje cells to neurotrophin treatment. J Neurochem 66:1362–1373

    Article  PubMed  CAS  Google Scholar 

  54. Doughty ML, Lohof A, Campana A, Delhaye-Bouchaud N, Mariani J (1998) Neurotrophin-3 promotes cerebellar granule cell exit from the EGL. Eur J Neurosci 10:3007–3011

    Article  PubMed  CAS  Google Scholar 

  55. Zhou P, Porcionatto M, Pilapil M, Chen Y, Choi Y, Tolias KF, Bikoff JB, Hong EJ, Greenberg ME, Segal RA (2007) Polarized signaling endosomes coordinate BDNF-induced chemotaxis of cerebellar precursors. Neuron 55:53–68

    Article  PubMed  CAS  Google Scholar 

  56. Jones KR, Farinas I, Backus C, Reichardt LF (1994) Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development. Cell 76:989–999

    Article  PubMed  CAS  Google Scholar 

  57. Schwartz PM, Borghesani PR, Levy RL, Pomeroy SL, Segal RA (1997) Abnormal cerebellar development and foliation in BDNF−/− mice reveals a role for neurotrophins in CNS patterning. Neuron 19:269–281

    Article  PubMed  CAS  Google Scholar 

  58. Carter AR, Chen C, Schwartz PM, Segal RA (2002) Brain-derived neurotrophic factor modulates cerebellar plasticity and synaptic ultrastructure. J Neurosci 22:1316–1327

    PubMed  CAS  Google Scholar 

  59. Bates B, Rios M, Trumpp A, Chen C, Fan G, Bishop JM, Jaenisch R (1999) Neurotrophin-3 is required for proper cerebellar development. Nat Neurosci 2:115–117

    Article  PubMed  CAS  Google Scholar 

  60. Courchesne E, Yeung-Courchesne R, Press GA, Hesselink JR, Jernigan TL (1988) Hypoplasia of cerebellar vermal lobules VI and VII in autism. N Engl J Med 318:1349–1354

    PubMed  CAS  Google Scholar 

  61. Pierce K, Courchesne E (2001) Evidence for a cerebellar role in reduced exploration and stereotyped behavior in autism. Biol Psychiatry 49:655–664

    Article  PubMed  CAS  Google Scholar 

  62. Martinez A, Alcantara S, Borrell V, Del Rio JA, Blasi J, Otal R, Campos N, Boronat A, Barbacid M, Silos-Santiago I, Soriano E (1998) TrkB and TrkC signaling are required for maturation and synaptogenesis of hippocampal connections. J Neurosci 18:7336–7350

    PubMed  CAS  Google Scholar 

  63. Ernfors P, Lee KF, Kucera J, Jaenisch R (1994) Lack of neurotrophin-3 leads to deficiencies in the peripheral nervous system and loss of limb proprioceptive afferents. Cell 77:503–512

    Article  PubMed  CAS  Google Scholar 

  64. World Health Organization (1992) The ICD-10 classification of mental and behavioural disorders: clinical descriptions and diagnostic guidelines. WHO, Geneva

    Google Scholar 

  65. American Psychiatric Association., American Psychiatric Association. Task Force on DSM-IV (1994) Diagnostic and statistical manual of mental disorders: DSM-IV, 4th edn. American Psychiatric Association, Washington, DC

    Google Scholar 

  66. Muhle R, Trentacoste SV, Rapin I (2004) The genetics of autism. Pediatrics 113:e472–486

    Article  PubMed  Google Scholar 

  67. Folstein SE, Rosen-Sheidley B (2001) Genetics of autism: complex aetiology for a heterogeneous disorder. Nat Rev Genet 2:943–955

    Article  PubMed  CAS  Google Scholar 

  68. Abrahams BS, Geschwind DH (2008) Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet 9:341–355

    Article  PubMed  CAS  Google Scholar 

  69. IMGSAC (2001) Further characterization of the autism susceptibility locus AUTS1 on chromosome 7q. Hum Mol Genet 10:973–982

    Article  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  71. Whitney ER, Kemper TL, Bauman ML, Rosene DL, Blatt GJ (2008) Cerebellar Purkinje cells are reduced in a subpopulation of autistic brains: a stereological experiment using calbindin-D28k. Cerebellum 7:406–416

    Article  PubMed  CAS  Google Scholar 

  72. Courchesne E, Pierce K, Schumann CM, Redcay E, Buckwalter JA, Kennedy DP, Morgan J (2007) Mapping early brain development in autism. Neuron 56:399–413

    Article  PubMed  CAS  Google Scholar 

  73. Takarae Y, Minshew NJ, Luna B, Krisky CM, Sweeney JA (2004) Pursuit eye movement deficits in autism. Brain 127:2584–2594

    Article  PubMed  Google Scholar 

  74. Manjiviona J, Prior M (1995) Comparison of Asperger syndrome and high-functioning autistic children on a test of motor impairment. J Autism Dev Disord 25:23–39

    Article  PubMed  CAS  Google Scholar 

  75. Casanova MF, Buxhoeveden D, Gomez J (2003) Disruption in the inhibitory architecture of the cell minicolumn: implications for autisim. Neuroscientist 9:496–507

    Article  PubMed  Google Scholar 

  76. Aman MG (2004) Management of hyperactivity and other acting-out problems in patients with autism spectrum disorder. Semin Pediatr Neurol 11:225–228

    Article  PubMed  Google Scholar 

  77. Aman MG, Langworthy KS (2000) Pharmacotherapy for hyperactivity in children with autism and other pervasive developmental disorders. J Autism Dev Disord 30:451–459

    Article  PubMed  CAS  Google Scholar 

  78. Richdale AL, Prior MR (1995) The sleep/wake rhythm in children with autism. Eur Child Adolesc Psychiatry 4:175–186

    Article  PubMed  CAS  Google Scholar 

  79. Filipek PA, Accardo PJ, Ashwal S, Baranek GT, Cook EH Jr., Dawson G, Gordon B, Gravel JS, Johnson CP, Kallen RJ, Levy SE, Minshew NJ, Ozonoff S, Prizant BM, Rapin I, Rogers SJ, Stone WL, Teplin SW, Tuchman RF, Volkmar FR (2000) Practice parameter: screening and diagnosis of autism: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Child Neurology Society. Neurology 55:468–479

    PubMed  CAS  Google Scholar 

  80. Deacon SW, Serpinskaya AS, Vaughan PS, Lopez Fanarraga M, Vernos I, Vaughan KT, Gelfand VI (2003) Dynactin is required for bidirectional organelle transport. J Cell Biol 160:297–301

    Article  PubMed  CAS  Google Scholar 

  81. Waterman-Storer CM, Karki SB, Kuznetsov SA, Tabb JS, Weiss DG, Langford GM, Holzbaur EL (1997) The interaction between cytoplasmic dynein and dynactin is required for fast axonal transport. Proc Natl Acad Sci U S A 94:12180–12185

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by grants-in-aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science, and Technology (MEXT), the Japan Science and Technology Agency (JST), the Japan Society for the Promotion of Science (JSPS), and the Institute of Physical and Chemical Research (RIKEN).

Author information

Authors and Affiliations

  1. Laboratory for Molecular Neurogenesis, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan

    Tetsushi Sadakata & Teiichi Furuichi

  2. JST, CREST, Kawaguchi, 332-0012, Japan

    Tetsushi Sadakata & Teiichi Furuichi

Authors
  1. Tetsushi Sadakata
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Teiichi Furuichi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Teiichi Furuichi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sadakata, T., Furuichi, T. Developmentally Regulated Ca2+-Dependent Activator Protein for Secretion 2 (CAPS2) is Involved in BDNF Secretion and is Associated with Autism Susceptibility. Cerebellum 8, 312–322 (2009). https://doi.org/10.1007/s12311-009-0097-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12311-009-0097-5

Keywords

Search

Navigation