Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex

Enrico Brugnera, Lisa Haney, Cynthia Grimsley, Mingjian Lu, Scott F. Walk, Annie Carole Tosello-Trampont, Ian G. Macara, Hiten Madhani, Gerald R. Fink, Kodimangalam S. Ravichandran

Research output: Contribution to journalArticlepeer-review

464 Scopus citations

Abstract

Mammalian Dock180 and ELMO proteins, and their homologues in Caenorhabditis elegans and Drosophila melanogaster, function as critical upstream regulators of Rac during development and cell migration. The mechanism by which Dock180 or ELMO mediates Rac activation is not understood. Here, we identify a domain within Dock180 (denoted Docker) that specifically recognizes nucleotide-free Rac and can mediate GTP loading of Rac in vitro. The Docker domain is conserved among known Dock180 family members in metazoans and in a yeast protein. In cells, binding of Dock180 to Rac alone is insufficient for GTP loading, and a Dock180-ELMO1 interaction is required. We can also detect a trimeric ELMO1-Dock180-Rac1 complex and ELMO augments the interaction between Dock180 and Rac. We propose that the Dock180-ELMO complex functions as an unconventional two-part exchange factor for Rac.

Original languageEnglish
Pages (from-to)574-582
Number of pages9
JournalNature Cell Biology
Volume4
Issue number8
DOIs
StatePublished - Aug 2002

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