What causes growth cone collapse?2018-02-06T10:37:47+08:30

What causes growth cone collapse?

Growth cone collapse is a complex phenomenon involving numerous signal pathways including Rho-GTPases [1], ADF [2], and various kinases [3][4]. A model for filopodia collapse in growth cones was created using the guidance signal, semaphorin IIIA (SemaIIIA; collapsin-1). SemaIIIA causes termination of protrusive activity and growth cone collapse [5] through decreased phosphorylation of the ezrin–radixin–moesin (ERM) family of F-actin binding proteins [6]. Phosphorylation of ERM proteins activates the F-actin binding domain and regulates filopodia assembly/protrusion by linking filopodial membranes with F-actin (reviewed in [7]). Inactivation of the phosphoinositide 3-kinase (PI3K) signal pathway by SemaIIIA may also be linked to reduced ERM protein activity and growth cone collapse [6].

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  1. Liu BP, and Strittmatter SM. Semaphorin-mediated axonal guidance via Rho-related G proteins. Curr. Opin. Cell Biol. 2001; 13(5):619-26. [PMID: 11544032]
  2. Aizawa H, Wakatsuki S, Ishii A, Moriyama K, Sasaki Y, Ohashi K, Sekine-Aizawa Y, Sehara-Fujisawa A, Mizuno K, Goshima Y, and Yahara I. Phosphorylation of cofilin by LIM-kinase is necessary for semaphorin 3A-induced growth cone collapse. Nat. Neurosci. 2001; 4(4):367-73. [PMID: 11276226]
  3. Sasaki Y, Cheng C, Uchida Y, Nakajima O, Ohshima T, Yagi T, Taniguchi M, Nakayama T, Kishida R, Kudo Y, Ohno S, Nakamura F, and Goshima Y. Fyn and Cdk5 mediate semaphorin-3A signaling, which is involved in regulation of dendrite orientation in cerebral cortex. Neuron 2002; 35(5):907-20. [PMID: 12372285]
  4. Eickholt BJ, Walsh FS, and Doherty P. An inactive pool of GSK-3 at the leading edge of growth cones is implicated in Semaphorin 3A signaling. J. Cell Biol. 2002; 157(2):211-7. [PMID: 11956225]
  5. Luo Y, Raible D, and Raper JA. Collapsin: a protein in brain that induces the collapse and paralysis of neuronal growth cones. Cell 1993; 75(2):217-27. [PMID: 8402908]
  6. Gallo G. Semaphorin 3A inhibits ERM protein phosphorylation in growth cone filopodia through inactivation of PI3K. Dev Neurobiol 2008; 68(7):926-33. [PMID: 18327764]
  7. Bretscher A, Edwards K, and Fehon RG. ERM proteins and merlin: integrators at the cell cortex. Nat. Rev. Mol. Cell Biol. 2002; 3(8):586-99. [PMID: 12154370]