Li CR, Au Yong JY, Wang YM, Wang Y.
Published in J Cell Sci. 2012 Feb 24. [Epub ahead of print]
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 Ser/Thr with Ala in these sites prevents Gin4 activation, weakens its association with Sep7, alters Sep7 dynamics and causes morphological and cytokinetic defects. In contrast, phosphomimetic mutation enhances the kinase activity with only moderate deteriorating effects. We also find that Gin4 has both kinase-independent and dependent functions acting during G1 and mitosis respectively, with the former being essential for septin ring assembly. Thus, our findings reveal a novel signaling pathway linking CDKs and the septins and provide new insights into the mechanisms controlling septin organization and function in coordination with cell-cycle phases.
Model of Cdc28 regulation of the septin complex.
Cdc28 regulates septin organization at two discrete times of the cell cycle: G1 and mitosis, and both intimately involve Gin4. Gin4's role in G1 does not require its kinase activity; instead it plays a structural role in cooperation with the Cdc42 module to promote septin ring assembly. In mitosis, Cdc28-Clb2 phosphorylates and activates Gin4 which in turn phosphorylates Sep7 regulating the property of the septin complex
For more information on Yue WANG's research, please click here.