Thioredoxin mediates oxidation-dependent phosphorylation of CRMP2 and growth cone collapse

Akifumi Morinaka, Mayumi Yamada, Rurika Itofusa, Yosuke Funato, Yuta Yoshimura, Fumio Nakamura, Takeshi Yoshimura, Kozo Kaibuchi, Yoshio Goshima, Mikio Hoshino, Hiroyuki Kamiguchi, Hiroaki Miki

研究成果: Article査読

77 被引用数 (Scopus)

抄録

Semaphorin3A (Sema3A) is a repulsive guidance molecule for axons, which acts by inducing growth cone collapse through phosphorylation of CRMP2 (collapsin response mediator protein 2). Here, we show a role for CRMP2 oxidation and thioredoxin (TRX) in the regulation of CRMP2 phosphorylation and growth cone collapse. Sema3A stimulation generated hydrogen peroxide (H 2O2) through MICAL (molecule interacting with CasL) and oxidized CRMP2, enabling it to form a disulfide-linked homodimer through cysteine-504. Oxidized CRMP2 then formed a transient disulfide-linked complex with TRX, which stimulated CRMP2 phosphorylation by glycogen synthase kinase-3, leading to growth cone collapse. We also reconstituted oxidation-dependent phosphorylation of CRMP2 in vitro, using a limited set of purified proteins. Our results not only clarify the importance of H2O2 and CRMP2 oxidation in Sema3A-induced growth cone collapse, but also indicate an unappreciated role for TRX in linking CRMP2 oxidation to phosphorylation.

本文言語English
論文番号ra26
ジャーナルScience Signaling
4
170
DOI
出版ステータスPublished - 26-04-2011
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学
  • 細胞生物学

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