Asef, a link between the tumor suppressor APC and G-protein signaling

The adenomatous polyposis coli gene (APC) is mutated in familiar adenomatou s polyposis and in sporadic colorectal tumors. Here the APC gene product is shown to bind through its armadillo repeat domain to a Rac-specific guanin e nucleotide exchange factor (GEF), termed Asef. Endogenous APC colocalized with Asef in mouse colon epithelial cells and neuronal cells. Furthermore, APC enhanced the CEF activity of Asef and stimulated Asef-mediated cell fl attening, membrane ruffling, and Lamellipodia formation in MDCK cells. Thes e results suggest that the APC-Asef complex may regulate the actin cytoskel etal network, cell morphology and migration, and neuronal function.