Indrajit Sinha, Yan-Ming Wang, Robin Philp, Chang-Run Li, Wai Ho Yap, and Yue Wang.
Cyclin-dependent kinases (Cdks) control cytoskeleton polarization in yeast morphogenesis. However, the target and mechanism remain unclear. Here, we show that the Candida albicans Cdk Cdc28, through temporally controlled association with two cyclins Ccn1 and Hgc1, rapidly establishes and persistently maintains phosphorylation of the septin cytoskeleton protein Cdc11 for hyphal development. Upon hyphal induction, Cdc28–Ccn1 binds to septin complexes and phosphorylates Cdc11 on Ser394, a nonconsensus Cdk target. This phosphorylation requires prior phosphorylation on Ser395 by the septin-associated kinase Gin4.
Mutating Ser394 or Ser395 blocked Cdc11 phosphorylation on Ser394 and impaired hyphal morphogenesis. Reconstitution experiments using purified Cdc28–Ccn1, Gin4, and septins reproduced phosphorylations on the same residues. Transient septin-Cdc28 associations were also detected prior to bud and mating-projection emergence in S. cerevisiae.
Our study uncovers a direct link between the cell-cycle engine and the septin cytoskeleton that may be part of a conserved mechanism underlying polarized morphogenesis.
Published in Dev Cell 13: 421-432, 2007.