Title of article :
CED-12/ELMO, a Novel Member of the CrkII/Dock180/Rac Pathway, Is Required for Phagocytosis and Cell Migration
Author/Authors :
Tina L. Gumienny، نويسنده , , Enrico Brugnera، نويسنده , , Annie-Carole Tosello-Trampont، نويسنده , , Jason M. Kinchen، نويسنده , , Lisa B. Haney، نويسنده , , Kiyoji Nishiwaki، نويسنده , , Scott F. Walk، نويسنده , , Michael E. Nemergut، نويسنده , , Ian G. Macara، نويسنده , , Ross Francis، نويسنده , , Tim Schedl، نويسنده , , Chunfei Li and Yi Qin، نويسنده , , Linda Van Aelst، نويسنده , , Michael O. Hengartner، نويسنده , , Kodimangalam S. Ravichandran، نويسنده ,
Abstract :
The C. elegans genes ced-2, ced-5, and ced-10, and their mammalian homologs crkII, dock180, and rac1, mediate cytoskeletal rearrangements during phagocytosis of apoptotic cells and cell motility. Here, we describe an additional member of this signaling pathway, ced-12, and its mammalian homologs, elmo1 and elmo2. In C. elegans, CED-12 is required for engulfment of dying cells and for cell migrations. In mammalian cells, ELMO1 functionally cooperates with CrkII and Dock180 to promote phagocytosis and cell shape changes. CED-12/ELMO-1 binds directly to CED-5/Dock180; this evolutionarily conserved complex stimulates a Rac-GEF, leading to Rac1 activation and cytoskeletal rearrangements. These studies identify CED-12/ELMO as an upstream regulator of Rac1 that affects engulfment and cell migration from C. elegans to mammals.
