Ral-regulated interaction between Sec5 and paxillin targets Exocyst to focal complexes during cell migration.
Ral-regulated interaction between Sec5 and paxillin targets Exocyst to focal complexes during cell migration.
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DOI:
10.1242/jcs.031641
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发表时间:
2008-09-01
影响因子:
4
通讯作者:
Yeaman C
中科院分区:
文献类型:
--
作者:
Spiczka KS;Yeaman C
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 likely 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 co-localizes 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 α5-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.
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DOI:
10.1083/jcb.153.7.1427
发表时间:
2001-06-25
期刊:
The Journal of cell biology
影响因子:
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作者:
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通讯作者:
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作者:
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11.4
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影响因子:
64.5
作者:
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DOI:
10.1073/pnas.94.26.14438
发表时间:
1997-12-23
影响因子:
11.1
作者:
Kee, Y;Yoo, JS;Scheller, RH
通讯作者:
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