Dock180 and ELMO1 proteins cooperate to promote evolutionarily conserved Rac-dependent cell migration.

TitleDock180 and ELMO1 proteins cooperate to promote evolutionarily conserved Rac-dependent cell migration.
Publication TypeJournal Article
Year of Publication2004
JournalThe Journal of biological chemistry
Volume279
Issue7
Pagination6087-97
Date Published2004 Feb 13
ISSN0021-9258
AbstractCell migration is essential throughout embryonic and adult life. In numerous cell systems, the small GTPase Rac is required for lamellipodia formation at the leading edge and movement ability. However, the molecular mechanisms leading to Rac activation during migration are still unclear. Recently, a mammalian superfamily of proteins related to the prototype member Dock180 has been identified with homologues in Drosophila and Caenorhabditis elegans. Here, we addressed the role of Dock180 and ELMO1 proteins, which function as a complex to mediate Rac activation, in mammalian cell migration. Using mutants of Dock180 and ELMO1 in a Transwell assay as well as transgenic rescue of a C. elegans mutant lacking CED-5 (Dock180 homologue), we identified specific regions of Dock180 and ELMO1 required for migration in vitro and in a whole animal model. In both systems, the Dock180.ELMO1 complex formation and the ability to activate Rac were required. We also found that ELMO1 regulated multiple Dock180 superfamily members to promote migration. Interestingly, deletion mutants of ELMO1 missing their first 531 or first 330 amino acids that can still bind and cooperate with Dock180 in Rac activation failed to promote migration, which correlated with the inability to localize to lamellipodia. This finding suggests that Rac activation by the ELMO.Dock180 complex at discrete intracellular locations mediated by the N-terminal 330 amino acids of ELMO1 rather than generalized Rac activation plays a role in cell migration.
URLhttp://www.jbc.org/cgi/pmidlookup?view=long&pmid=14638695
DOI10.1074/jbc.M307087200
PubMed Linkhttp://www.ncbi.nlm.nih.gov/pubmed/14638695?dopt=Abstract
Short TitleJ Biol Chem