NOVEL CDC42-BINDING PROTEINS GIC1 AND GIC2 CONTROL CELL POLARITY IN YEAST

Cdc42p, a Rho-related GTP-binding protein, regulates cytoskeletal pola rization and rearrangements in eukaryotic cells, but the effecters med iating this control remain unknown. Through the use of the complete ye ast genomic sequence, we have identified two novel Cdc42p targets, Gic 1p and Gic2p, which contain consensus Cdc42/Rac interactive-binding (C RIB) domains and bind specifically to Cdc42p-GTP. Gic1p and Gic2p colo calize with Cdc42p as cell polarity is established during the cell cyc le and during mating in response to pheromones. Cells deleted for both GIC genes exhibit defects in actin and microtubule polarization simil ar to those observed in cdc42 mutants. finally, the interaction of the Gic proteins and Cdc42p is essential, as mutations in the CRIB domain of Gic2p that eliminate Cdc42p binding disrupt Gic2p localization and function. Thus, Gic1p and Gic2p define a novel class of Cdc42p target s that are specifically required for cytoskeletal polarization in vivo .