期刊
EMBO JOURNAL
卷 27, 期 18, 页码 2375-2387出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2008.166
关键词
cytokinesis; exocyst; Ral GTPases; RalGEFs
资金
- Association de Recherche sur la Cancer (ARC) [3131]
- Agence Nationale de la Recherche (ANR) [ANR05BLAN033802]
- National Cancer Institute [CA129451]
- Robert Welch foundation [I-1414]
- EMBO
- Institut National du Cancer (INCa)
The Ras family G-proteins RalA and RalB make critical non-overlapping contributions to the generation of a tumorigenic regulatory network, supporting bypass of the normal restraints on both cell proliferation and survival. The Sec6/8 complex, or exocyst, has emerged as a principal direct effector complex for Ral GTPases. Here, we show that RalA and RalB support mitotic progression through mobilization of the exocyst for two spatially and kinetically distinct steps of cytokinesis. RalA is required to tether the exocyst to the cytokinetic furrow in early cytokinesis. RalB is then required for recruitment of the exocyst to the midbody of this bridge to drive abscission and completion of cytokinesis. The collaborative action of RalA and RalB is specified by discrete subcellular compartmentalization and unique pairs of RalGEF proteins that provide inputs from both Ras-family protein-dependent and protein-independent regulatory cues. This suggests that Ral GTPases integrate diverse upstream signals to choreograph multiple roles for the exocyst in mitotic progression.
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