title: CDK regulates septin organization through cell-cycle-dependent phosphorylation of the Nim1-related kinase Gin4.
abstract: Cyclin-dependent kinases (CDKs) regulate septin organization in a cell-cycle-dependent manner in yeast. However, the mechanism remains unclear. Here, we show that the Candida albicans CDK Cdc28 phosphorylates the Nim1-related kinase Gin4, a known septin regulator, activating its kinase activity, which in turn phosphorylates the Sep7 septin. Gin4 contains a cluster of CDK phosphorylation sites near the kinase domain. Replacing serine/threonine with alanine in these sites prevents Gin4 activation, weakens its association with Sep7, alters Sep7 dynamics and causes morphological and cytokinetic defects. By contrast, phosphomimetic mutation enhances the kinase activity with only moderate deteriorating effects. We also found that Gin4 has both kinase-independent and -dependent functions, acting during G1 phase and mitosis, respectively, with the former being essential for septin ring assembly. Thus, we have identified a previously unknown signaling pathway linking CDKs and the septins that provides new insights into the mechanisms controlling septin organization and function in coordination with cell-cycle phases.
authors.affiliation: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Proteos, 61 Biopolis Drive, 138673,  Singapore.
authors.forename: Chang-Run
authors.initials: CR
authors.lastname: Li
authors.forename: Jie-Ying
authors.initials: JY
authors.lastname: Au Yong
authors.forename: Yan-Ming
authors.initials: YM
authors.lastname: Wang
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
mesh_terms: D002176:Candida albicans / Q000166:cytology / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D010766:Phosphorylation
chemical_list: D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D018844:Cyclin-Dependent Kinases