The DOCK180/Elmo complex couples ARNO-mediated Arf6 activation to the downstream activation of Rac1

Lorraine C. Santy, Kodi S. Ravichandran, James E. Casanova

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

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 Dock180/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 β-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.

Original languageEnglish (US)
Pages (from-to)1749-1754
Number of pages6
JournalCurrent Biology
Volume15
Issue number19
DOIs
StatePublished - Oct 11 2005

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ADP-Ribosylation Factors
Madin Darby Canine Kidney Cells
Chemical activation
guanosinetriphosphatase
microfilaments
Actin Cytoskeleton
mutants
pseudopodia
Pseudopodia
Monomeric GTP-Binding Proteins
GTP Phosphohydrolases
cells
cell movement
Cell Movement
plasma membrane
Actins
Cell Membrane
Cell membranes

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences(all)

Cite this

Santy, Lorraine C. ; Ravichandran, Kodi S. ; Casanova, James E. / The DOCK180/Elmo complex couples ARNO-mediated Arf6 activation to the downstream activation of Rac1. In: Current Biology. 2005 ; Vol. 15, No. 19. pp. 1749-1754.
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The DOCK180/Elmo complex couples ARNO-mediated Arf6 activation to the downstream activation of Rac1. / Santy, Lorraine C.; Ravichandran, Kodi S.; Casanova, James E.

In: Current Biology, Vol. 15, No. 19, 11.10.2005, p. 1749-1754.

Research output: Contribution to journalArticle

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