Cdc28-Cln3 phosphorylation of Sla1 regulates actin patch dynamics in different modes of fungal growth.
A dynamic balance between targeted transport and endocytosis is critical for polarized cell growth. However, how actin-mediated endocytosis is regulated in different growth modes remains unclear. Here we report differential regulation of cortical actin patch dynamics between the yeast and hyphal growth in Candida albicans. The mechanism involves phosphoregulation of the endocytic protein Sla1 by the cyclin-dependent kinase (CDK) Cdc28-Cln3 and the actin-regulating kinase Prk1. Mutational studies of the CDK phosphorylation sites of Sla1 revealed that Cdc28-Cln3 phosphorylation of Sla1 enhances its further phosphorylation by Prk1, weakening Sla1 association with Pan1, an activator of the actin-nucleating Arp2/3 complex. Sla1 is rapidly dephosphorylated upon hyphal induction and remains so throughout hyphal growth. Consistently, cells expressing a phosphomimetic version of Sla1 exhibited markedly reduced actin patch dynamics, impaired endocytosis, and defective hyphal development, whereas a nonphosphorylatable Sla1 had the opposite effect. Taken together, our findings establish a molecular link between CDK and a key component of the endocytic machinery, revealing a novel mechanism by which endocytosis contributes to cell morphogenesis.
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673.
Guisheng
G
Zeng
Yan-Ming
YM
Wang
Yue
Y
Wang
D008841:Actin Cytoskeleton / Q000378:metabolism; D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D042846:CDC2-CDC28 Kinases / Q000378:metabolism*; D002176:Candida albicans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D025301:Hyphae / Q000254:growth & development; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*
D051376:Actin-Related Protein 2-3 Complex; D048868:Adaptor Proteins, Signal Transducing; D016213:Cyclins; D003598:Cytoskeletal Proteins; D005656:Fungal Proteins; C061570:protein kinase N; D011493:Protein Kinase C; D042846:CDC2-CDC28 Kinases