βPix Guanine Nucleotide Exchange Factor Regulates Regeneration of Injured Peripheral Axons

Yewon Jeon, Yoon Kyung Shin, Hwigyeong Kim, Yun Young Choi, Minjae Kang, Younghee Kwon, Yongcheol Cho, Sung Wook Chi, Jung Eun Shin

Research output: Contribution to journalArticlepeer-review

Abstract

Axon regeneration is essential for successful recovery after peripheral nerve injury. Although growth cone reformation and axonal extension are crucial steps in axonal regeneration, the regulatory mechanisms underlying these dynamic processes are poorly understood. Here, we identify βPix (Arhgef7), the guanine nucleotide exchange factor for Rac1 GTPase, as a regulator of axonal regeneration. After sciatic nerve injury in mice, the expression levels of βPix increase significantly in nerve segments containing regenerating axons. In regrowing axons, βPix is localized in the peripheral domain of the growth cone. Using βPix neuronal isoform knockout (NIKO) mice in which the neuronal isoforms of βPix are specifically removed, we demonstrate that βPix promotes neurite outgrowth in cultured dorsal root ganglion neurons and in vivo axon regeneration after sciatic nerve crush injury. Activation of cJun and STAT3 in the cell bodies is not affected in βPix NIKO mice, supporting the local action of βPix in regenerating axons. Finally, inhibiting Src, a kinase previously identified as an activator of the βPix neuronal isoform, causes axon outgrowth defects in vitro, like those found in the βPix NIKO neurons. Altogether, these data indicate that βPix plays an important role in axonal regrowth during peripheral nerve regeneration.

Original languageEnglish
Article number14357
JournalInternational journal of molecular sciences
Volume24
Issue number18
DOIs
Publication statusPublished - 2023 Sept

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Keywords

  • Rac1
  • Src
  • axon regeneration
  • dorsal root ganglion
  • growth cone
  • guanine nucleotide exchange factor
  • sciatic nerve injury
  • small GTPase

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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