Cell Cycle Checkpoints

Sensing Septins at the Bud

Science's STKE  30 Sep 2003:
Vol. 2003, Issue 202, pp. tw385-TW385
DOI: 10.1126/stke.2003.202.tw385

Eukaryotic cells clearly monitor and respond to variations in the organization of the cytoskeleton, but the precise sensors that are used are not well understood. In yeast cells, septin proteins must be organized into filaments in a ring-like structure at a site where a bud forms and where cytokinesis eventually pinches off the daughter cells. If septins are not properly assembled, a checkpoint mechanism is engaged that delays progression of the cell division cycle so that cells do not undergo mitosis. The protein kinase Hsl1 is activated in cells with properly assembled septins and transmits a signal that promotes entry into mitosis. Hanrahan and Snyder now report that this kinase itself appears to function as a sensor of septin status. They show that, like many kinases, Hsl1 contains an autoinhibitory domain that binds to and inhibits activity of the catalytic domain. Two-hybrid analysis showed that this same kinase inhibitory domain also contains multiple septin-binding domains. In vitro, presence of autoinhibitory fragment inhibited catalytic activity of the intact kinase, and addition of septins relieved this inhibition. In vivo, mutants in which the septin-binding domains were disrupted were morphologically similar to mutants lacking Hsl1. Thus, the protein kinase Hsl1 appears to sense septin organization directly at the bud and then to phosphorylate substrates that promote progression through mitosis.

J. Hanrahan, M. Snyder, Cytoskeletal activation of a checkpoint kinase. Mol. Cell 12, 663-673 (2003). [Online Journal]