Roles of STEF/Tiam1, guanine nucleotide exchange factors for Rac1, in regulation of growth cone morphology

Naoki Matsuo, Mami Terao, Yo Ichi Nabeshima, Mikio Hoshino

研究成果: Contribution to journalArticle査読

44 被引用数 (Scopus)

抄録

Rho family GTPases are suggested to be pivotal for growth cone behavior, but regulation of their activities in response to environmental cues remains elusive. Here, we describe roles of STEF and Tiam1, guanine nucleotide exchange factors for Rac1, in neurite growth and growth cone remodeling. We reveal that, in primary hippocampal neurons, STEF/Tiam1 are localized within growth cones and essential for formation of growth cone lamellipodia, eventually contributing to neurite growth. Furthermore, experiments using a dominant-negative form demonstrate that STEF/Tiam1 mediate extracellular laminin signals to activate Rac1, promoting neurite growth in N1E-115 neuroblastoma cells. STEF/Tiam1 are revealed to mediate Cdc42 signal to activate Rac1 during lamellipodial formation. We also show that RhoA inhibits the STEF/Tiam1-Rac1 pathway. These data are used to propose a model that extracellular and intracellular information is integrated by STEF/Tiam1 to modulate the balance of Rho GTPase activities in the growth cone and, consequently, to control growth cone behavior.

本文言語英語
ページ(範囲)69-81
ページ数13
ジャーナルMolecular and Cellular Neuroscience
24
1
DOI
出版ステータス出版済み - 9 1 2003
外部発表はい

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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