期刊
CURRENT BIOLOGY
卷 22, 期 2, 页码 147-153出版社
CELL PRESS
DOI: 10.1016/j.cub.2011.11.058
关键词
-
资金
- Institut PASTEUR [G5]
- CNRS
- Agence Nationale pour la Recherche (ANR) [ANR07-JCJC-0089]
- Schlumberger Foundation for Education and Research
- Institut Curie
- Ministere de la Recherche et de l'Enseignement Superieur
- Ecole Doctorale Complexite du Vivant
- Association pour la Recherche sur le Cancer
- Grants-in-Aid for Scientific Research [20113006] Funding Source: KAKEN
Cytokinesis bridge instability leads to binucleated cells that can promote tumorigenesis in vivo [1]. Membrane trafficking is crucial for animal cell cytokinesis [2-8], and several endocytic pathways regulated by distinct GTPases (Rab11, Rab21, Rab35, ARF6, RalA/B) [9-16] contribute to the post-furrowing steps of cytokinesis. However, little is known about how these pathways are coordinated for successful cytokinesis. The Rab35 GTPase controls a fast endocytic recycling pathway and must be activated for SEPTIN cytoskeleton localization at the intercellular bridge, and thus for completion of cytokinesis [12]. Here, we report that the ARF6 GTPase [17,18] negatively regulates Rab35 activation and hence the Rab35 pathway. Human cells expressing a constitutively activated, GTP-bound ARF6 mutant display identical endocytic recycling and cytokinesis defects as those observed upon overexpression of the inactivated, GDP-bound Rab35 mutant. As a molecular mechanism, we identified the Rab35 GAP EP164B as an effector of ARF6 in negatively regulating Rab35 activation. Unexpectedly, this regulation takes place at clathrin-coated pits, and activated ARF6 reduces Rab35 loading into the endocytic pathway. Thus, an effector of an ARF protein is a GAP for a downstream Rab protein, and we propose that this hierarchical ARF/Rab GTPase cascade controls the proper activation of a common endocytic pathway essential for cytokinesis.
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