CED-12/ELMO, a novel member of the crkII/dock180/rac pathway, is required for phagocytosis and cell migration

The C. elegans genes ced-2, ced-5, and ced-10, and their mammalian homologs crkII, dock180, and rac1, mediate cytoskeletal rearrangements during phago cytosis of apoptotic cells and cell motility. Here, we describe an addition al member of this signaling pathway, ced-12, and its mammalian homologs, el mo1 and elmo2. In C. elegans, CED-12 is required for engulfment of dying ce lls and for cell migrations. In mammalian cells, ELMO1 functionally coopera tes with CrkII and Dock180 to promote phagocytosis and cell shape changes. CED-12/ELMO-1 binds directly to CED-5/ Dock180; this evolutionarily conserv ed complex stimulates a Rac-GEF, leading to Rac1 activation and cytoskeleta l rearrangements. These studies identify CED-12/ELMO as an upstream regulat or of Rac1 that affects engulfment and cell migration from C. elegans to ma mmals.