Three C-elegans Rac proteins and several alternative Rac regulators control axon guidance, cell migration and apoptotic cell phagocytosis

The Caenorhabditis elegans genome contains three rac-like genes, ced-10, mi g-2, and rac-2. We report that ced-10, mig-2 and rac-2 act redundantly in a xon pathfinding: inactivating one gene had little effect, but inactivating two or more genes perturbed both axon outgrowth and guidance. mig-2 and ced -10 also have redundant functions in some cell migrations. By contrast, ced -10 is uniquely required for cell-corpse phagocytosis, and mig-2 and rac-2 have only subtle roles in this process. Rac activators are also used differ entially. The UNC-73 Trio Rac GTP exchange factor affected all Rac pathways in axon pathfinding and cell migration but did not affect cell-corpse phag ocytosis. CED-5 DOCK180, which acts with CED-10 Rac in cell-corpse phagocyt osis, acted with MIG-2 but not CED-10 in axon pathfinding. Thus, distinct r egulatory proteins modulate Rac activation and function in different develo pmental processes.