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First published online 12 August 2008
doi: 10.1242/jcs.031641

Journal of Cell Science 121, 2880-2891 (2008)
Published by The Company of Biologists 2008
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Research Article

Ral-regulated interaction between Sec5 and paxillin targets Exocyst to focal complexes during cell migration

Krystle S. Spiczka and Charles Yeaman*

Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA

* Author for correspondence (e-mail: charles-yeaman{at}uiowa.edu)

Accepted 16 June 2008

Changes in cellular behavior that cause epithelial cells to lose adhesiveness, acquire a motile invasive phenotype and metastasize to secondary sites are complex and poorly understood. Molecules that normally function to integrate adhesive spatial information with cytoskeleton dynamics and membrane trafficking probably serve important functions in cellular transformation. One such complex is the Exocyst, which is essential for targeted delivery of membrane and secretory proteins to specific plasma membrane sites to maintain epithelial cell polarity. Upon loss of cadherin-mediated adhesion in Dunning R3327-5'A prostate tumor cells, Exocyst localization shifts from lateral membranes to tips of protrusive membrane extensions. Here, it colocalizes and co-purifies with focal complex proteins that regulate membrane trafficking and cytoskeleton dynamics. These sites are the preferred destination of post-Golgi transport vesicles ferrying biosynthetic cargo, such as {alpha}5-integrin, which mediates adhesion of cells to the substratum, a process essential to cell motility. Interference with Exocyst activity impairs integrin delivery to plasma membrane and inhibits tumor cell motility and matrix invasiveness. Localization of Exocyst and, by extension, targeting of Exocyst-dependent cargo, is dependent on Ral GTPases, which control association between Sec5 and paxillin. Overexpression of Ral-uncoupled Sec5 mutants inhibited Exocyst interaction with paxillin in 5'A cells, as did RNAi-mediated reduction of either RalA or RalB. Reduction of neither GTPase significantly altered steady-state levels of assembled Exocyst in these cells, but did change the observed localization of Exocyst proteins.

Key words: Cell motility, Cell polarity, Exocyst, Metastasis, Ral




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K. S. Spiczka and C. Yeaman
Ral-regulated interaction between Sec5 and paxillin targets Exocyst to focal complexes during cell migration
Development, September 15, 2008; 135(18): e1 - e1.
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