Novel Cdc42-binding proteins Gic1 and Gic2 control cell polarity in yeast.
Cdc42p, a Rho-related GTP-binding protein, regulates cytoskeletal polarization and rearrangements in eukaryotic cells, but the effectors mediating this control remain unknown. Through the use of the complete yeast genomic sequence, we have identified two novel Cdc42p targets, Gic1p and Gic2p, which contain consensus Cdc42/Rac interactive-binding (CRIB) domains and bind specifically to Cdc42p-GTP. Gic1p and Gic2p colocalize with Cdc42p as cell polarity is established during the cell cycle and during mating in response to pheromones. Cells deleted for both GIC genes exhibit defects in actin and microtubule polarization similar 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 targets that are specifically required for cytoskeletal polarization in vivo.
Brown
J L
JL
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Jaquenoud
M
M
Gulli
M P
MP
Chant
J
J
Peter
M
M
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology*; D002451:Cell Compartmentation; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000502:physiology*; D016764:Cell Polarity; D003599:Cytoskeleton / Q000648:ultrastructure; D005656:Fungal Proteins / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D020690:GTPase-Activating Proteins; D005800:Genes, Fungal; D006160:Guanosine Triphosphate / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae
D048868:Adaptor Proteins, Signal Transducing; C084219:BEM2 protein, S cerevisiae; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; C109252:GIC1 protein, S cerevisiae; C109253:GIC2 protein, S cerevisiae; D020690:GTPase-Activating Proteins; D029701:Saccharomyces cerevisiae Proteins; C073129:BEM1 protein, S cerevisiae; D006160:Guanosine Triphosphate; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae