Characterization of STEF, a guanine nucleotide exchange factor for Rac1, required for neurite growth

Naoki Matsuo, Mikio Hoshino, Masato Yoshizawa, Yo Ichi Nabeshima

研究成果: Contribution to journalArticle査読

68 被引用数 (Scopus)

抄録

Accumulating evidence suggests that Rho family GTPases play critical roles in the organization of the nervous system. We previously identified a guanine nucleotide exchange factor of Rac1, STEF (SIF and Tiam 1-like exchange factor), which can induce ruffling membrane in KB cells and is predominantly expressed in the brain during development. Here, we characterize the molecular nature of STEF and its involvement in neurite growth. Deletion analyses revealed distinct roles for individual domains: PHnTSS for membrane association, DH for enzymatic activity, and PHc for promoting catalytic activity. Ectopic expression of STEF in NIE-115 neuroblastoma cells induced neurite-like processes containing F-actin, βIII tubulin, MAP2, and GAP43 in a Rac1-dependent manner even under the serum-containing neurite-inhibiting conditions. We further found that a PHnTSS STEF fragment specifically inhibited the function of both STEF and Tiam1, a closely related Rac1 guanine nucleotide exchange factor. Suppression of endogenous STEF and Tiam1 activities in N1E-115 cells by ectopically expressed PHnTSS STEF resulted in inhibition of neurite outgrowth in serum-starved conditions, which usually induce neurite formation. Furthermore, these inhibitory effects were rescued by exogenously expressed STEF or Tiam1, suggesting that STEF and Tiaml are involved in neurite formation through the activation of Rac1 and successive cytoskeletal reorganization of neuronal cells during development.

本文言語英語
ページ(範囲)2860-2868
ページ数9
ジャーナルJournal of Biological Chemistry
277
4
DOI
出版ステータス出版済み - 1 25 2002
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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