Article
- The EMBO Journal (2008) 27, 2375 - 2387
- doi:10.1038/emboj.2008.166
Published online: 28 August 2008
Subject Categories:
Distinct roles of RalA and RalB in the progression of cytokinesis are supported by distinct RalGEFs
Ilaria Cascone1, Rasim Selimoglu1, Cafer Ozdemir2, Elaine Del Nery3, Charles Yeaman4, Michael White2 and Jacques Camonis1,3
- Institut Curie, Paris, France
- Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX, USA
- The Biophenics Automated Imaging Laboratory, Department of Translational Biology, Institut Curie, Paris, France
- Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IO, USA
Correspondence to:
Jacques Camonis, Institut Curie, Inserm U830, 26 rue d'Ulm, 75248 Paris cedex 05, France. Tel.: +33 1 4234 6654; Fax: +33 1 4234 6650; E-mail: jcamonis@curie.fr
Received 3 February 2008; Accepted 31 July 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.
Keywords:
- cytokinesis,
- exocyst,
- Ral GTPases,
- RalGEFs
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