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Regulation of Axon Formation

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Handbook of Neurochemistry and Molecular Neurobiology

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Abstract

A mature neuron is typically polarized with a single long axon and several dendrites. After the birth and differentiation of a neuron, a neuron breaks its previous symmetry and establishes an axon and dendrites. Neuronal polarization occurs when one of the multiple immature neurites emerging from the cell body elongates rapidly. This neurite becomes the axon, whereas the remaining immature neurites become dendrites. What are the molecular mechanisms specifying the axon in the initial events? Here we provide an overview of recent progress into the study of axon formation.

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Abbreviations

APC:

adenomatous polyposis coli

aPKC:

atypical protein kinase C

CRMP-2:

collapsin response mediator protein-2

GEF:

guanine nucleotide exchange factor

GSK-3β:

glycogen synthase kinase-3β

ILK:

integrin-linked kinase

NgCAM:

neuron-glia cell adhesion molecule

PI3-kinase:

phosphatidylinositol 3-kinase

PIP3 :

phosphatidylinositol 3,4,5-triphosphate

PTEN:

phosphatase and tensin homolog deleted on chromosome 10

siRNA:

short interfering RNA

Sra-1:

specifically Rac1-associated protein 1

STEF:

Sif- and Tiam1-like exchange factor

Tiam1:

T-lymphoma invasion and metastasis 1

References

  • Andersen SS, Bi GQ. 2000. Axon formation: A molecular model for the generation of neuronal polarity. Bioessays 22: 172–179.

    Article  CAS  PubMed  Google Scholar 

  • Arimura N, Menager C, Fukata Y, Kaibuchi K. 2004. Role of CRMP-2 in neuronal polarity. J Neurobiol 58: 34–47.

    Article  CAS  PubMed  Google Scholar 

  • Arimura N, Menager C, Kawano Y, Yoshimura T, Kawabata S, et al. 2005. Phosphorylation by Rho kinase regulates CRMP-2 activity in growth cones. Mol Cell Biol 25: 9973–9984.

    Article  CAS  PubMed  Google Scholar 

  • Arimura N, Kaibuchi K. 2007. Neuronal polarity: From extracellular signals to intracellular mechanisms. Nat Rev Neurosci 8: 194–205.

    Article  CAS  PubMed  Google Scholar 

  • Baas PW. 1997. Microtubules and axonal growth. Curr Opin Cell Biol 9: 29–36.

    Article  CAS  PubMed  Google Scholar 

  • Baas PW, Buster DW. 2004. Slow axonal transport and the genesis of neuronal morphology. J Neurobiol 58: 3–17.

    Article  CAS  PubMed  Google Scholar 

  • Bradke F, Dotti CG. 1999. The role of local actin instability in axon formation. Science 283: 1931–1934.

    Article  CAS  PubMed  Google Scholar 

  • Bradke F, Dotti CG. 2000a. Establishment of neuronal polarity: Lessons from cultured hippocampal neurons. Curr Opin Neurobiol 10: 574–581.

    Article  CAS  PubMed  Google Scholar 

  • Bradke F, Dotti CG. 2000b. Differentiated neurons retain the capacity to generate axons from dendrites. Curr Biol 10: 1467–1470.

    Article  CAS  PubMed  Google Scholar 

  • Brown A, Slaughter T, Black MM. 1992. Newly assembled microtubules are concentrated in the proximal and distal regions of growing axons. J Cell Biol 119: 867–882.

    Article  CAS  PubMed  Google Scholar 

  • Brown A, Li Y, Slaughter T, Black MM. 1993. Composite microtubules of the axon: Quantitative analysis of tyrosinated and acetylated tubulin along individual axonal microtubules. J Cell Sci 104: 339–352.

    CAS  PubMed  Google Scholar 

  • Cowan CR, Hyman AA. 2004. Asymmetric cell division in C. elegans: Cortical polarity and spindle positioning. Annu Rev Cell Dev Biol 20: 427–453.

    Article  CAS  PubMed  Google Scholar 

  • Craig AM, Banker G. 1994. Neuronal polarity. Annu Rev Neurosci 17: 267–310.

    Article  CAS  PubMed  Google Scholar 

  • Dotti CG, Banker GA. 1987. Experimentally induced alteration in the polarity of developing neurons. Nature 330: 254–256.

    Article  CAS  PubMed  Google Scholar 

  • Dotti CG, Sullivan CA, Banker GA. 1988. The establishment of polarity by hippocampal neurons in culture. J Neurosci 8: 1454–1468.

    CAS  PubMed  Google Scholar 

  • Esch T, Lemmon V, Banker G. 1999. Local presentation of substrate molecules directs axon specification by cultured hippocampal neurons. J Neurosci 19: 6417–6426.

    CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Fukata Y, Itoh TJ, Kimura T, Menager C, Nishimura T, et al. 2002. CRMP-2 binds to tubulin heterodimers to promote microtubule assembly. Nat Cell Biol 4: 583–591.

    CAS  PubMed  Google Scholar 

  • Goold RG, Owen R, Gordon-Weeks PR. 1999. Glycogen synthase kinase 3β phosphorylation of microtubule-associated protein 1B regulates the stability of microtubules in growth cones. J Cell Sci 112: 3373–3384.

    CAS  PubMed  Google Scholar 

  • Goshima Y, Nakamura F, Strittmatter P, Strittmatter SM. 1995. Collapsin-induced growth cone collapse mediated by an intracellular protein related to UNC-33. Nature 376: 509–514.

    Article  CAS  PubMed  Google Scholar 

  • Goslin K, Banker G. 1989. Experimental observations on the development of polarity by hippocampal neurons in culture. J Cell Biol 108: 1507–1516.

    Article  CAS  PubMed  Google Scholar 

  • Govek EE, Newey SE, Van Aelst L. 2005. The role of the Rho GTPases in neuronal development. Genes Dev 19: 1–49.

    Article  CAS  PubMed  Google Scholar 

  • Grimes CA, Jope RS. 2001. The multifaceted roles of glycogen synthase kinase 3β in cellular signaling. Prog Neurobiol 65: 391–426.

    Article  CAS  PubMed  Google Scholar 

  • Hannigan G, Troussard AA, Dedhar S. 2005. Integrin-linked kinase: A cancer therapeutic target unique among its ILK. Nat Rev Cancer 5: 51–63.

    Article  CAS  PubMed  Google Scholar 

  • Hedgecock EM, Culotti JG, Thomson JN, Perkins LA. 1985. Axonal guidance mutants of Caenorhabditis elegans identified by filling sensory neurons with fluorescein dyes. Dev Biol 111: 158–170.

    Article  CAS  PubMed  Google Scholar 

  • Horiguchi K, Hanada T, Fukui Y, Chishti AH 2006. Transport of PIP3 by GAKIN, a kinesin-3 family protein, regulates neuronal cell polarity. J Cell Biol 174: 425–436.

    Article  CAS  PubMed  Google Scholar 

  • Iijima M, Huang YE, Devreotes P. 2002. Temporal and spatial regulation of chemotaxis. Dev Cell 3: 469–478.

    Article  CAS  PubMed  Google Scholar 

  • Inagaki N, Chihara K, Arimura N, Menager C, Kawano Y, et al. 2001. CRMP-2 induces axons in cultured hippocampal neurons. Nat Neurosci 4: 781–782.

    Article  CAS  PubMed  Google Scholar 

  • Jacobs T, Causeret F, Nishimura YV, Terao M, Norman A, et al. 2007. Localized activation of p21-activated kinase controls neuronal polarity and morphology. J Neurosci 27: 8604–8615.

    Article  CAS  PubMed  Google Scholar 

  • Jacobson C, Schnapp B, Banker GA. 2006. A change in the selective translocation of the Kinesin-1 motor domain marks the initial specification of the axon. Neuron 49: 797–804.

    Article  CAS  PubMed  Google Scholar 

  • Jiang H, Guo W, Liang X, Rao Y. 2005. Both the establishment and the maintenance of neuronal polarity require active mechanisms: Critical roles of GSK-3β and its upstream regulators. Cell 120: 123–135.

    CAS  PubMed  Google Scholar 

  • Kawano Y, Yoshimura T, Tsuboi D, Kawabata S, Kaneko-Kawano T, et al. 2005. CRMP-2 is involved in Kinesin-1-dependent transport of the Sra-1/WAVE1 complex and axon formation. Mol Cell Biol 25: 9920–9935.

    Article  CAS  PubMed  Google Scholar 

  • Kimura T, Arimura N, Fukata Y, Watanabe H, Iwamatsu A, et al. 2005. Tubulin and CRMP-2 complex is transported via Kinesin-1. J Neurochem 93: 1371–1382.

    Article  CAS  PubMed  Google Scholar 

  • Kunda P, Paglini G, Quiroga S, Kosik K, Caceres A. 2001. Evidence for the involvement of Tiam1 in axon formation. J Neurosci 21: 2361–2372.

    CAS  PubMed  Google Scholar 

  • Macara IG. 2004. Parsing the polarity code. Nat Rev Mol Cell Biol 5: 220–231.

    Article  CAS  PubMed  Google Scholar 

  • Maehama T, Dixon JE. 1998. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 273: 13375–13378.

    Article  CAS  PubMed  Google Scholar 

  • Menager C, Arimura N, Fukata Y, Kaibuchi K. 2004. PIP3 is involved in neuronal polarization and axon formation. J Neurochem 89: 109–118.

    Article  CAS  PubMed  Google Scholar 

  • Nakata T, Hirokawa N. 2003. Microtubules provide directional cues for polarized axonal transport through interaction with kinesin motor head. J Cell Biol 162: 1045–1055.

    Article  CAS  PubMed  Google Scholar 

  • Nishimura T, Fukata Y, Kato K, Yamaguchi T, Matsuura Y, et al. 2003. CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth. Nat Cell Biol 5: 819–826.

    Article  CAS  PubMed  Google Scholar 

  • Nishimura T, Kato K, Yamaguchi T, Fukata Y, Ohno S, et al. 2004. Role of the PAR-3-KIF3 complex in the establishment of neuronal polarity. Nat Cell Biol 6: 328–334.

    Article  CAS  PubMed  Google Scholar 

  • Nishimura T, Yamaguchi T, Kato K, Yoshizawa M, Nabeshima Y, et al. 2005. PAR-6-PAR-3 mediates Cdc42-induced Rac activation through the Rac GEFs STEF/Tiam1. Nat Cell Biol 7: 270–277.

    Article  CAS  PubMed  Google Scholar 

  • Ohno S. 2001. Intercellular junctions and cellular polarity: The PAR–aPKC complex, a conserved core cassette playing fundamental roles in cell polarity. Curr Opin Cell Biol 13: 641–648.

    Article  CAS  PubMed  Google Scholar 

  • Oinuma I, Katoh H, Negishi M. 2007. R-Ras controls axon specification upstream of glycogen synthase kinase-3beta through integrin-linked kinase. J Biol Chem 282: 303–318.

    Article  CAS  PubMed  Google Scholar 

  • Scheid MP, Woodgett JR. 2001. PKB/AKT: Functional insights from genetic models. Nat Rev Mol Cell Biol 2: 760–768.

    Article  CAS  PubMed  Google Scholar 

  • Schmidt A, Hall A. 2002. Guanine nucleotide exchange factors for Rho GTPases: Turning on the switch. Genes Dev 16: 1587–1609.

    Article  CAS  PubMed  Google Scholar 

  • Schwamborn JC, Puschel AW. 2004. The sequential activity of the GTPases Rap1B and Cdc42 determines neuronal polarity. Nat Neurosci 7: 923–929.

    Article  CAS  PubMed  Google Scholar 

  • Shi SH, Jan LY, Jan YN. 2003. Hippocampal neuronal polarity specified by spatially localized mPar3/mPar6 and PI 3-kinase activity. Cell 112: 63–75.

    Article  CAS  PubMed  Google Scholar 

  • Takei Y, Teng J, Harada A, Hirokawa N. 2000. Defects in axonal elongation and neuronal migration in mice with disrupted tau and map1b genes. J Cell Biol 150: 989–1000.

    Article  CAS  PubMed  Google Scholar 

  • Toriyama M, Shimada T, Kim KB, Mitsuba M, Nomura E, et al. 2006. Shootin1: A protein involved in the organization of an asymmetric signal for neuronal polarization. J Cell Biol 175: 147–157.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Wang LH, Strittmatter SM. 1996. A family of rat CRMP genes is differentially expressed in the nervous system. J Neurosci 16: 6197–6207.

    CAS  PubMed  Google Scholar 

  • Watabe-Uchida M, John KA, Janas JA, Newey SE, Van Aelst L. 2006. The Rac activator DOCK7 regulates neuronal polarity through local phosphorylation of stathmin/Op18. Neuron 51: 727–739.

    Article  CAS  PubMed  Google Scholar 

  • Yan D, Guo L, Wang Y. 2006. Requirement of dendritic Akt degradation by the ubiquitin-proteasome system for neuronal polarity. J Cell Biol 174: 415–424.

    Article  CAS  PubMed  Google Scholar 

  • Yoshimura T, Kawano Y, Arimura N, Kawabata S, Kikuchi A, et al. 2005. GSK-3β regulates phosphorylation of CRMP-2 and neuronal polarity. Cell 120: 137–149.

    Article  CAS  PubMed  Google Scholar 

  • Yoshimura T, Arimura N, Kawano Y, Kawabata S, Wang S, et al. 2006. Ras regulates neuronal polarity via the PI3-kinase/Akt/GSK-3β/CRMP-2 pathway. Biochem Biophys Res Commun 340: 62–68.

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Zhu J, Yang GY, Wang QJ, Qian L, et al. 2007. Dishevelled promotes axon differentiation by regulating atypical protein kinase C. Nat Cell Biol 9: 743–754.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Zumbrunn J, Kinoshita K, Hyman AA, Nathke IS. 2001. Binding of the adenomatous polyposis coli protein to microtubules increases microtubule stability and is regulated by GSK3β phosphorylation. Curr Biol 11: 44–49.

    Article  CAS  PubMed  Google Scholar 

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Authors
  1. T. Yoshimura
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  2. N. Arimura
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  3. K. Kaibuchi
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Editor information

Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 10962, 140 Old Orangeburg Road, Orangeburg, New York, USA

    Abel Lajtha (Director) (Director)

  2. Group Director of Neuro-Developmental Disorder Research Group, RIKEN Brain Science Institute, 351-0198, 2-1 Hirosawa Wako-shi, Saitama, Japan

    Katsuhiko Mikoshiba

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Yoshimura, T., Arimura, N., Kaibuchi, K. (2009). Regulation of Axon Formation. In: Lajtha, A., Mikoshiba, K. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30370-3_3

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