Phosphorylation of the Cdc42 exchange factor Cdc24 by the PAK-like kinase Cla4 may regulate polarized growth in yeast.
Rho-type GTPases control many cytoskeletal rearrangements, but their regulation remains poorly understood. Here, we show that in S. cerevisiae, activation of the CDK Cdc28-Cln2 at bud emergence triggers relocalization of Cdc24, the GEF for Cdc42, from the nucleus to the polarization site, where it is stably maintained by binding to the adaptor Bem1. Locally activated Cdc42 then polarizes the cytoskeleton in a manner dependent on its effectors Bni1 and the PAK-like kinase Cla4. In addition, Cla4 induces phosphorylation of Cdc24, leading to its dissociation from Bem1 at bud tips, thereby ending polarized bud growth in vivo. Our results thus suggest a dynamic temporal and spatial regulation of the Cdc42 module: Cdc28-Cln triggers actin polarization by activating Cdc42, which in turn restricts its own activation via a negative feedback loop acting on its GEF Cdc24.
Gulli
M P
MP
Swiss Institute for Experimental Cancer Research Chemin des Boveresses 155 1066 Epalinges, Vaud, Switzerland.
Jaquenoud
M
M
Shimada
Y
Y
Niederhäuser
G
G
Wiget
P
P
Peter
M
M
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D017489:CDC28 Protein Kinase, S cerevisiae / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D016764:Cell Polarity; D016213:Cyclins / Q000378:metabolism; D022083:Cytoplasmic Structures / Q000737:chemistry / Q000378:metabolism; D003599:Cytoskeleton / Q000737:chemistry / Q000378:metabolism; D004789:Enzyme Activation; D025461:Feedback, Physiological; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D016193:G1 Phase; D020662:Guanine Nucleotide Exchange Factors; D006160:Guanosine Triphosphate / Q000378:metabolism; D046911:Macromolecular Substances; D008840:Microfilament Proteins; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C105191:Bni1 protein, S cerevisiae; C073594:CDC24 protein, S cerevisiae; C082721:CLN2 protein, S cerevisiae; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; D005656:Fungal Proteins; C109253:GIC2 protein, S cerevisiae; D020662:Guanine Nucleotide Exchange Factors; D046911:Macromolecular Substances; D008840:Microfilament Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C073129:BEM1 protein, S cerevisiae; D006160:Guanosine Triphosphate; C095212:CLA4 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D017489:CDC28 Protein Kinase, S cerevisiae; D020764:cdc42 GTP-Binding Protein