期刊
CURRENT BIOLOGY
卷 15, 期 19, 页码 1749-1754出版社
CELL PRESS
DOI: 10.1016/j.cub.2005.08.052
关键词
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资金
- NIGMS NIH HHS [GM-66251, GM064709] Funding Source: Medline
Cell motility requires extensions of the plasma membrane driven by reorganization of the actin cytoskeleton. Small GTPases, particularly the Rho family, are key regulators of this process [1-3]. A second class of GTPases, the ADP-ribosylation factors (ARFs), have also been implicated in the regulation of the actin cytoskeleton and motility [4]. ARF6 is intimately involved in the regulation of Rac activity [5-9]; however, the mechanisms by which ARF activation leads to activation of Rac remain poorly understood. We have previously shown that expression of the ARF-GEF ARNO in MDCK cells induces robust activation of Rac, the formation of large lamellipodia, and the onset of motility [9]. We report here that ARNO-dependent activation of Rac is mediated by a bipartite Rac GEF, the Dock1 80/Elmo complex. Both DOCK180 and Elmo colocalize extensively with ARNO in migrating MDCK cells. Importantly, both a catalytically inactive Dock180 mutant and an Elmo mutant that fails to couple to Dock180 block ARNO-induced Rac activation and motility. In contrast, a similar mutant of the Rac GEF beta-PIX fails to inhibit ARNO-induced Rac activation or motility. Together, these data suggest that ARNO and ARF6 coordinate with the Dock180/Elmo complex to promote Rac activation at the leading edge of migrating cells.
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