The C. elegans gene ced-12
functions in the engulfment of apoptotic cells and in cell migration, acting in a signaling pathway with ced-2
DOCK180, and ced-10
Rac GTPase and acting upstream of ced-10
encodes a protein with a pleckstrin homology (PH) domain and an SH3 binding motif, both of which are important for ced-12
function. CED-12 acts in engulfing cells for cell corpse engulfment and interacts physically with CED-5, which contains an SH3 domain. CED-12 has Drosophila and human counterparts. Expression of CED-12 and its counterparts in murine Swiss 3T3 fibroblasts induced Rho GTPase-dependent formation of actin filament bundles. We propose that through interactions with membranes and with a CED-2/CED-5 protein complex, CED-12 regulates Rho/Rac GTPase signaling and leads to cytoskeletal reorganization by an evolutionarily conserved mechanism.