Abstract
Neurons undergo various morphologic changes during development, including neuritogenesis, neurite outgrowth, neurite branching, and neurite retraction. Many studies have examined how microtubules (MTs) are reorganized or transported within the neurites of developing neurons and have revealed that MT dynamics are regulated by MT-interacting proteins and motor proteins, in concert with actin microfilaments. Here, I will describe recent progress in research on the behavior of MTs in the nervous system.
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Acebes A, Ferrus A (2000) Cellular and molecular features of axon collaterals and dendrites. Trends Neurosci 23:557–565
Ahmad FJ, Hughey J, Wittmann T, Hyman A, Greaser M, Baas PW (2000) Motor proteins regulate force interactions between microtubules and microfilaments in the axon. Nat Cell Biol 2:276–280
Akhmanova A, Steinmetz MO (2008) Tracking the ends: a dynamic protein network controls the fate of microtubule tips. Nat Rev Mol Cell Biol 9:309–322
Arimura N, Kaibuchi K (2007) Neuronal polarity: from extracellular signals to intracellular mechanisms. Nat Rev Neurosci 8:194–205
Baas PW, Ahmad FJ (2001) Force generation by cytoskeletal motor proteins as a regulator of axonal elongation and retraction. Trends Cell Biol 11:244–249
Baas PW, Deitch JS, Black MM, Banker GA (1988) Polarity orientation of microtubules in hippocampal neurons: uniformity in the axon and nonuniformity in the dendrite. Proc Natl Acad Sci USA 85:8335–8339
Baas PW, Vidya Nadar C, Myers KA (2006) Axonal transport of microtubules: the long and short of it. Traffic 7:490–498
Bahi-Buisson N, Poirier K, Boddaert N, Saillour Y, Castelnau L, Philip N, Buyse G, Villard L, Joriot S, Marret S, Bourgeois M, Van Esch H, Lagae L, Amiel J, Hertz-Pannier L, Roubertie A, Rivier F, Pinard JM, Beldjord C, Chelly J (2008) Refinement of cortical dysgeneses spectrum associated with TUBA1A mutations. J Med Genet 45:647–653
Benitez-King G, Ramirez-Rodriguez G, Ortiz L, Meza I (2004) The neuronal cytoskeleton as a potential therapeutical target in neurodegenerative diseases and schizophrenia. Curr Drug Targets CNS Neurol Disord 3:515–533
Bouquet C, Ravaille-Veron M, Propst F, Nothias F (2007) MAP1B coordinates microtubule and actin filament remodeling in adult mouse Schwann cell tips and DRG neuron growth cones. Mol Cell Neurosci 36:235–247
Bradke F, Dotti CG (1999) The role of local actin instability in axon formation. Science 283:1931–1934
Burnette DT, Ji L, Schaefer AW, Medeiros NA, Danuser G, Forscher P (2008) Myosin II activity facilitates microtubule bundling in the neuronal growth cone neck. Dev Cell 15:163–169
Burnette DT, Schaefer AW, Ji L, Danuser G, Forscher P (2007) Filopodial actin bundles are not necessary for microtubule advance into the peripheral domain of Aplysia neuronal growth cones. Nat Cell Biol 9:1360–1369
Chevalier-Larsen E, Holzbaur EL (2006) Axonal transport and neurodegenerative disease. Biochim Biophys Acta 1762:1094–1108
Corbo JC, Deuel TA, Long JM, LaPorte P, Tsai E, Wynshaw-Boris A, Walsh CA (2002) Doublecortin is required in mice for lamination of the hippocampus but not the neocortex. J Neurosci 22:7548–7557
da Silva JS, Dotti CG (2002) Breaking the neuronal sphere: regulation of the actin cytoskeleton in neuritogenesis. Nat Rev Neurosci 3:694–704
Dawson HN, Ferreira A, Eyster MV, Ghoshal N, Binder LI, Vitek MP (2001) Inhibition of neuronal maturation in primary hippocampal neurons from tau deficient mice. J Cell Sci 114:1179–1187
de Anda FC, Pollarolo G, Da Silva JS, Camoletto PG, Feiguin F, Dotti CG (2005) Centrosome localization determines neuronal polarity. Nature 436:704–708
Dehmelt L, Smart FM, Ozer RS, Halpain S (2003) The role of microtubule-associated protein 2c in the reorganization of microtubules and lamellipodia during neurite initiation. J Neurosci 23:9479–9490
Dent EW, Barnes AM, Tang F, Kalil K (2004) Netrin-1 and semaphorin 3A promote or inhibit cortical axon branching, respectively, by reorganization of the cytoskeleton. J Neurosci 24:3002–3012
Dent EW, Callaway JL, Szebenyi G, Baas PW, Kalil K (1999) Reorganization and movement of microtubules in axonal growth cones and developing interstitial branches. J Neurosci 19:8894–8908
Dent EW, Gertler FB (2003) Cytoskeletal dynamics and transport in growth cone motility and axon guidance. Neuron 40:209–227
Dent EW, Kalil K (2001) Axon branching requires interactions between dynamic microtubules and actin filaments. J Neurosci 21:9757–9769
Dixit R, Ross JL, Goldman YE, Holzbaur EL (2008) Differential regulation of dynein and kinesin motor proteins by tau. Science 319:1086–1089
Dompierre JP, Godin JD, Charrin BC, Cordelieres FP, King SJ, Humbert S, Saudou F (2007) Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington’s disease by increasing tubulin acetylation. J Neurosci 27:3571–3583
Dotti CG, Sullivan CA, Banker GA (1988) The establishment of polarity by hippocampal neurons in culture. J Neurosci 8:1454–1468
El-Kadi AM, Soura V, Hafezparast M (2007) Defective axonal transport in motor neuron disease. J Neurosci Res 85:2557–2566
Erez H, Malkinson G, Prager-Khoutorsky M, De Zeeuw CI, Hoogenraad CC, Spira ME (2007) Formation of microtubule-based traps controls the sorting and concentration of vesicles to restricted sites of regenerating neurons after axotomy. J Cell Biol 176:497–507
Erturk A, Hellal F, Enes J, Bradke F (2007) Disorganized microtubules underlie the formation of retraction bulbs and the failure of axonal regeneration. J Neurosci 27:9169–9180
Etienne-Manneville S, Hall A (2003) Cell polarity: Par6, aPKC and cytoskeletal crosstalk. Curr Opin Cell Biol 15:67–72
Fallet-Bianco C, Loeuillet L, Poirier K, Loget P, Chapon F, Pasquier L, Saillour Y, Beldjord C, Chelly J, Francis F (2008) Neuropathological phenotype of a distinct form of lissencephaly associated with mutations in TUBA1A. Brain 131:2304–2320
Feng J (2006) Microtubule: a common target for parkin and Parkinson’s disease toxins. Neuroscientist 12:469–476
Forscher P, Smith SJ (1988) Actions of cytochalasins on the organization of actin filaments and microtubules in a neuronal growth cone. J Cell Biol 107:1505–1516
Fukushima N (2004) LPA in neural cell development. J Cell Biochem 92:993–1003
Fukushima N, Furuta D, Hidaka Y, Moriyama R, Tsujiuchi T (2009) Posttranslational modifications of tubulin in the nervous system. J Neurochem 109:683–693
Fukushima N, Morita Y (2006) Actomyosin-dependent microtubule rearrangement in lysophosphatidic acid-induced neurite remodeling of young cortical neurons. Brain Res 1094:65–75
Fukushima N, Weiner JA, Kaushal D, Contos JJA, Rehen SK, Kingsbury MA, Kim K-Y, Chun J (2002) Lysophosphatidic acid influences the morphology and motility of young, postmitotic cortical neurons. Mol Cell Neurosci 20:271–282
Galjart N (2005) CLIPs and CLASPs and cellular dynamics. Nat Rev Mol Cell Biol 6:487–498
Gallo G, Letourneau PC (1999) Different contributions of microtubule dynamics and transport to the growth of axons and collateral sprouts. J Neurosci 19:3860–3873
Georges PC, Hadzimichalis NM, Sweet ES, Firestein BL (2008) The yin-yang of dendrite morphology: unity of actin and microtubules. Mol Neurobiol 38:270–284
Gerdes JM, Katsanis N (2005) Small molecule intervention in microtubule-associated human disease. Hum Mol Genet 14(Spec No 2):R291–R300
Grabham PW, Seale GE, Bennecib M, Goldberg DJ, Vallee RB (2007) Cytoplasmic dynein and LIS1 are required for microtubule advance during growth cone remodeling and fast axonal outgrowth. J Neurosci 27:5823–5834
Gu J, Firestein BL, Zheng JQ (2008) Microtubules in dendritic spine development. J Neurosci 28:12120–12124
Gundersen GG, Cook TA (1999) Microtubules and signal transduction. Curr Opin Cell Biol 11:81–94
Hammond JW, Cai D, Verhey KJ (2008) Tubulin modifications and their cellular functions. Curr Opin Cell Biol 20:71–76
Hasaka TP, Myers KA, Baas PW (2004) Role of actin filaments in the axonal transport of microtubules. J Neurosci 24:11291–11301
He Y, Francis F, Myers KA, Yu W, Black MM, Baas PW (2005) Role of cytoplasmic dynein in the axonal transport of microtubules and neurofilaments. J Cell Biol 168:697–703
He Y, Yu W, Baas PW (2002) Microtubule reconfiguration during axonal retraction induced by nitric oxide. J Neurosci 22:5982–5991
Higuchi M, Lee VM, Trojanowski JQ (2002) Tau and axonopathy in neurodegenerative disorders. Neuromolecular Med 2:131–150
Hollenbeck P (2001) Cytoskeleton: microtubules get the signal. Curr Biol 11:R820–R823
Hu X, Viesselmann C, Nam S, Merriam E, Dent EW (2008) Activity-dependent dynamic microtubule invasion of dendritic spines. J Neurosci 28:13094–13105
Jaworski J, Hoogenraad CC, Akhmanova A (2008) Microtubule plus-end tracking proteins in differentiated mammalian cells. Int J Biochem Cell Biol 40:619–637
Jimenez-Mateos EM, Wandosell F, Reiner O, Avila J, Gonzalez-Billault C (2005) Binding of microtubule-associated protein 1B to LIS1 affects the interaction between dynein and LIS1. Biochem J 389:333–341
Kalil K, Dent EW (2005) Touch and go: guidance cues signal to the growth cone cytoskeleton. Curr Opin Neurobiol 15:521–526
Keays DA, Tian G, Poirier K, Huang GJ, Siebold C, Cleak J, Oliver PL, Fray M, Harvey RJ, Molnar Z, Pinon MC, Dear N, Valdar W, Brown SD, Davies KE, Rawlins JN, Cowan NJ, Nolan P, Chelly J, Flint J (2007) Mutations in alpha-tubulin cause abnormal neuronal migration in mice and lissencephaly in humans. Cell 128:45–57
Kerjan G, Gleeson JG (2007) Genetic mechanisms underlying abnormal neuronal migration in classical lissencephaly. Trends Genet 23:623–630
Kholmanskikh SS, Koeller HB, Wynshaw-Boris A, Gomez T, Letourneau PC, Ross ME (2006) Calcium-dependent interaction of Lis1 with IQGAP1 and Cdc42 promotes neuronal motility. Nat Neurosci 9:50–57
Lee H, Engel U, Rusch J, Scherrer S, Sheard K, Van Vactor D (2004) The microtubule plus end tracking protein Orbit/MAST/CLASP acts downstream of the tyrosine kinase Abl in mediating axon guidance. Neuron 42:913–926
Leung CL, Green KJ, Liem RK (2002) Plakins: a family of versatile cytolinker proteins. Trends Cell Biol 12:37–45
Lewis SA, Lee MG, Cowan NJ (1985) Five mouse tubulin isotypes and their regulated expression during development. J Cell Biol 101:852–861
Michaelis ML, Seyb KI, Ansar S (2005) Cytoskeletal integrity as a drug target. Curr Alzheimer Res 2:227–229
Mimori-Kiyosue Y, Grigoriev I, Lansbergen G, Sasaki H, Matsui C, Severin F, Galjart N, Grosveld F, Vorobjev I, Tsukita S, Akhmanova A (2005) CLASP1 and CLASP2 bind to EB1 and regulate microtubule plus-end dynamics at the cell cortex. J Cell Biol 168:141–153
Morris-Rosendahl DJ, Najm J, Lachmeijer AM, Sztriha L, Martins M, Kuechler A, Haug V, Zeschnigk C, Martin P, Santos M, Vasconcelos C, Omran H, Kraus U, Van der Knaap MS, Schuierer G, Kutsche K, Uyanik G (2008) Refining the phenotype of α-1a Tubulin (TUBA1A) mutation in patients with classical lissencephaly. Clin Genet 74:425–433
Ohkawa N, Fujitani K, Tokunaga E, Furuya S, Inokuchi K (2007) The microtubule destabilizer stathmin mediates the development of dendritic arbors in neuronal cells. J Cell Sci 120:1447–1456
Ohkawa N, Sugisaki S, Tokunaga E, Fujitani K, Hayasaka T, Setou M, Inokuchi K (2008) N-acetyltransferase ARD1-NAT1 regulates neuronal dendritic development. Genes Cells 13:1171–1183
Outeiro TF, Kontopoulos E, Altmann SM, Kufareva I, Strathearn KE, Amore AM, Volk CB, Maxwell MM, Rochet JC, McLean PJ, Young AB, Abagyan R, Feany MB, Hyman BT, Kazantsev AG (2007) Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson’s disease. Science 317:516–519
Palazzo AF, Joseph HL, Chen YJ, Dujardin DL, Alberts AS, Pfister KK, Vallee RB, Gundersen GG (2001) Cdc42, dynein, and dynactin regulate MTOC reorientation independent of Rho-regulated microtubule stabilization. Curr Biol 11:1536–1541
Paylor R, Hirotsune S, Gambello MJ, Yuva-Paylor L, Crawley JN, Wynshaw-Boris A (1999) Impaired learning and motor behavior in heterozygous Pafah1b1 (Lis1) mutant mice. Learn Mem 6:521–537
Riederer BM (2007) Microtubule-associated protein 1B, a growth-associated and phosphorylated scaffold protein. Brain Res Bull 71:541–558
Rodriguez OC, Schaefer AW, Mandato CA, Forscher P, Bement WM, Waterman-Storer CM (2003) Conserved microtubule-actin interactions in cell movement and morphogenesis. Nat Cell Biol 5:599–609
Roger B, Al-Bassam J, Dehmelt L, Milligan RA, Halpain S (2004) MAP2c, but not tau, binds and bundles F-actin via its microtubule binding domain. Curr Biol 14:363–371
Schaefer AW, Kabir N, Forscher P (2002) Filopodia and actin arcs guide the assembly and transport of two populations of microtubules with unique dynamic parameters in neuronal growth cones. J Cell Biol 158:139–152
Schaefer AW, Schoonderwoert VT, Ji L, Mederios N, Danuser G, Forscher P (2008) Coordination of actin filament and microtubule dynamics during neurite outgrowth. Dev Cell 15:146–162
Shano S, Hatanaka K, Ninose S, Moriyama R, Tsujiuchi T, Fukushima N (2008) A lysophosphatidic acid receptor lacking the PDZ-binding domain is constitutively active and stimulates cell proliferation. Biochim Biophys Acta 1783:748–759
Sonnenberg A, Liem RK (2007) Plakins in development and disease. Exp Cell Res 313:2189–2203
Stanchi F, Corso V, Scannapieco P, Ievolella C, Negrisolo E, Tiso N, Lanfranchi G, Valle G (2000) TUBA8: a new tissue-specific isoform of α-tubulin that is highly conserved in human and mouse. Biochem Biophys Res Commun 270:1111–1118
Stokin GB, Goldstein LS (2006) Axonal transport and Alzheimer’s disease. Annu Rev Biochem 75:607–627
Stoothoff WH, Johnson GV (2005) Tau phosphorylation: physiological and pathological consequences. Biochim Biophys Acta 1739:280–297
Stroissnigg H, Trancikova A, Descovich L, Fuhrmann J, Kutschera W, Kostan J, Meixner A, Nothias F, Propst F (2007) S-nitrosylation of microtubule-associated protein 1B mediates nitric-oxide-induced axon retraction. Nat Cell Biol 9:1035–1045
Suzuki K, Koike T (2007) Mammalian Sir2-related protein (SIRT) 2-mediated modulation of resistance to axonal degeneration in slow Wallerian degeneration mice: a crucial role of tubulin deacetylation. Neuroscience 147:599–612
Trivedi N, Marsh P, Goold RG, Wood-Kaczmar A, Gordon-Weeks PR (2005) Glycogen synthase kinase-3β phosphorylation of MAP1B at Ser1260 and Thr1265 is spatially restricted to growing axons. J Cell Sci 118:993–1005
Villasante A, Wang D, Dobner P, Dolph P, Lewis SA, Cowan NJ (1986) Six mouse α-tubulin mRNAs encode five distinct isotypes: testis-specific expression of two sister genes. Mol Cell Biol 6:2409–2419
Wang L, Brown A (2002) Rapid movement of microtubules in axons. Curr Biol 12:1496–1501
Westermann S, Weber K (2003) Post-translational modifications regulate microtubule function. Nat Rev Mol Cell Biol 4:938–947
Witte H, Neukirchen D, Bradke F (2008) Microtubule stabilization specifies initial neuronal polarization. J Cell Biol 180:619–632
Yamada KM, Spooner BS, Wessells NK (1970) Axon growth: roles of microfilaments and microtubules. Proc Natl Acad Sci USA 66:1206–1212
Yamada KM, Spooner BS, Wessells NK (1971) Ultrastructure and function of growth cones and axons of cultured nerve cells. J Cell Biol 49:614–635
Yu W, Ahmad FJ, Baas PW (1994) Microtubule fragmentation and partitioning in the axon during collateral branch formation. J Neurosci 14:5872–5884
Yu W, Qiang L, Solowska JM, Karabay A, Korulu S, Baas PW (2008) The microtubule-severing proteins spastin and katanin participate differently in the formation of axonal branches. Mol Biol Cell 19:1485–1498
Zhou FQ, Waterman-Storer CM, Cohan CS (2002) Focal loss of actin bundles causes microtubule redistribution and growth cone turning. J Cell Biol 157:839–849
Zhou FQ, Zhou J, Dedhar S, Wu YH, Snider WD (2004) NGF-induced axon growth is mediated by localized inactivation of GSK-3β and functions of the microtubule plus end binding protein APC. Neuron 42:897–912
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Fukushima, N. (2011). Microtubules in the Nervous System. In: Nixon, R., Yuan, A. (eds) Cytoskeleton of the Nervous System. Advances in Neurobiology, vol 3. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6787-9_2
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