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Molecular and Cellular Biology, January 2006, p. 727-734, Vol. 26, No. 2
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.2.727-734.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

RalB Mobilizes the Exocyst To Drive Cell Migration{dagger}

Carine Rossé,1 Anastassia Hatzoglou,1 Maria-Carla Parrini,1 Michael A. White,2 Philippe Chavrier,3 and Jacques Camonis1*

Institut Curie, Inserm U528, Transduction Networks Analysis Group, Paris, France,1 Department of Cell Biology, UT Southwestern Medical Center, Dallas, Texas,2 CNRS UMR144, Institut Curie, Paris, France3

Received 24 April 2005/ Returned for modification 16 May 2005/ Accepted 21 October 2005

The Ras family GTPases RalA and RalB have been defined as central components of the regulatory machinery supporting tumor initiation and progression. Although it is known that Ral proteins mediate oncogenic Ras signaling and physically and functionally interact with vesicle trafficking machinery, their mechanistic contribution to oncogenic transformation is unknown. Here, we have directly evaluated the relative contribution of Ral proteins and Ral effector pathways to cell motility and directional migration. Through loss-of-function analysis, we find that RalA is not limiting for cell migration in normal mammalian epithelial cells. In contrast, RalB and the Sec6/8 complex or exocyst, an immediate downstream Ral effector complex, are required for vectorial cell motility. RalB expression is required for promoting both exocyst assembly and localization to the leading edge of moving cells. We propose that RalB regulation of exocyst function is required for the coordinated delivery of secretory vesicles to the sites of dynamic plasma membrane expansion that specify directional movement.

* Corresponding author. Mailing address: Institut Curie, Inserm U528, 26 rue d'Ulm, 75248 Paris cedex 05, France. Phone: 33 1 42 34 66 54. Fax: 33 1 42 34 66 50. E-mail: Jacques.Camonis{at}curie.fr.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, January 2006, p. 727-734, Vol. 26, No. 2
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.2.727-734.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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