TC10, a Rho family GTPase, is required for efficient axon regeneration in a neuron-autonomous manner

Shingo Koinuma, Ryota Negishi, Riko Nomura, Kazuki Sato, Takuya Kojima, Eri Segi-Nishida, Ryo Goitsuka, Yoichiro Iwakura, Naoyuki Wada, Yoshiki Koriyama, Sumiko Kiryu-Seo, Hiroshi Kiyama, Takeshi Nakamura

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Intracellular signaling pathways that promote axon regeneration are closely linked to the mechanism of neurite outgrowth. TC10, a signaling molecule that acts on neurite outgrowth through membrane transport, is a member of the Rho family G proteins. Axon injury increases the TC10 levels in motor neurons, suggesting that TC10 may be involved in axon regeneration. In this study, we tried to understand the roles of TC10 in the nervous system using TC10 knock-out mice. In cultured hippocampal neurons, TC10 ablation significantly reduced axon elongation without affecting ordinary polarization. We determined a role of TC10 in microtubule stabilization at the growth cone neck; therefore, we assume that TC10 limits axon retraction and promotes in vitro axon outgrowth. In addition, there were no notable differences in the size and structure of brains during prenatal and postnatal development between wild-type and TC10 knock-out mice. In motor neurons, axon regeneration after injury was strongly suppressed in mice lacking TC10 (both in conventional and injured nerve specific deletion). In retinal ganglion cells, TC10 ablation suppressed the axon regeneration stimulated by intraocular inflammation and cAMP after optic nerve crush. These results show that TC10 plays an important role in axon regeneration in both the peripheral and central nervous systems, and the role of TC10 in peripheral axon regeneration is neuron-intrinsic. (Figure presented.).

Original languageEnglish
Pages (from-to)1196-1206
Number of pages11
JournalJournal of Neurochemistry
Volume157
Issue number4
DOIs
Publication statusPublished - May 2021

Keywords

  • Rho GTPase
  • TC10
  • axon outgrowth
  • axon regeneration
  • knock-out mice
  • membrane traffic

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