期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 16, 页码 7586-7591出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0914514107
关键词
Dock family proteins; brain-derived neurotrophic factor; Fyn; axonal regeneration; optic nerve
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Ministry of Health, Labour, and Welfare of Japan
- Uehara Memorial Foundation
- Naito Foundation
- Suzuken Memorial Foundation
- Daiwa Securities Health Foundation
- Takeda Science Foundation
- Japan Medical Association
Atypical Rho-guanine nucleotide exchange factors (Rho-GEFs) that contain Dock homology regions (DHR-1 and DHR-2) are expressed in a variety of tissues; however, their functions and mechanisms of action remain unclear. We identify key conserved amino acids in the DHR-2 domain that are critical for the catalytic activity of Dock-GEFs (Dock1-4). We further demonstrate that Dock-GEFs directly associate with WASP family verprolin-homologous (WAVE) proteins through the DHR-1 domain. Brain-derived neurotrophic factor (BDNF)-TrkB signaling recruits the Dock3/WAVE1 complex to the plasma membrane, whereupon Dock3 activates Rac and dissociates from the WAVE complex in a phosphorylation-dependent manner. BDNF induces axonal sprouting through Dock-dependent Rac activation, and adult transgenic mice overexpressing Dock3 exhibit enhanced optic nerve regeneration after injury without affecting WAVE expression levels. Our results highlight a unique mechanism through which Dock-GEFs achieve spatial and temporal restriction of WAVE signaling, and identify Dock-GEF activity as a potential therapeutic target for axonal regeneration.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据