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Distinct roles of RalA and RalB in the progression of cytokinesis are supported by distinct RalGEFs.
- Source :
-
The EMBO journal [EMBO J] 2008 Sep 17; Vol. 27 (18), pp. 2375-87. Date of Electronic Publication: 2008 Aug 28. - Publication Year :
- 2008
-
Abstract
- 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.
- Subjects :
- Cell Nucleus metabolism
Cell Proliferation
Cell Survival
HeLa Cells
Humans
Kinetics
Mitosis
Models, Biological
Vesicular Transport Proteins metabolism
ral GTP-Binding Proteins metabolism
ras Proteins metabolism
Cytokinesis
Gene Expression Regulation
ral GTP-Binding Proteins physiology
ral Guanine Nucleotide Exchange Factor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2075
- Volume :
- 27
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- The EMBO journal
- Publication Type :
- Academic Journal
- Accession number :
- 18756269
- Full Text :
- https://doi.org/10.1038/emboj.2008.166