IQGAP1, A RAC-BINDING AND CDC42-BINDING PROTEIN, DIRECTLY BINDS AND CROSS-LINKS MICROFILAMENTS

Activated forms of the GTPases, Rac and Cdc42, are known to stimulate formation of microfilament-rich Iamellipodia and filopodia, respective ly, but the underlying mechanisms have remained obscure. We now report the purification and characterization of a protein, IQGAP1, which is likely to mediate effects of these GTPases on microfilaments. Native I QGAP1 purified from bovine adrenal comprises two similar to 190-kD sub units per molecule plus substoichiometric calmodulin. Purified IQGAP1 bound directly to F-actin and cross-linked the actin filaments into ir regular, interconnected bundles that exhibited gel-like properties. En ogenous calmodulin partially inhibited binding of IQGAP1 to F-actin, a nd was more effective in the absence, than in the presence of calcium. Immunofluorescence microscopy demonstrated cytochalasin D-sensitive c olocalization of IQGAP1 with cortical microfilaments. These results, i n conjunction with prior evidence that IQGAP1 binds directly to activa ted Rac and Cdc42, suggest that IQGAP1 serves as a direct molecular li nk between these GTPases and the actin cytoskeleton, and that the acti n-binding activity of IQGAP1 is regulated by calmodulin.