Cell size is coordinated with cell division through regulation of the cyclin-dependent kinase Cdk1. Cdk1 activity is inhibited through its phosphorylation by the kinase Wee1, itself inhibited by the kinases Cdr1 and Cdr2; however, the signals that convey the crucial information about cell size to regulate Wee1 activity have been unclear (see Sawin). Now two groups, Moseley et al. and Martin and Berthelot-Grosjean, have combined genetic analysis with fluorescence imaging to implicate a gradient of the protein kinase Pom1 in coordinating the two in the rod-shaped fission yeast Schizosaccharomyces pombe. Yeast lacking Pom1 divided at a shorter length than did wild-type cells, whereas yeast with even a modest increase in Pom1 divided at longer lengths. Genetic analysis indicated that Pom1 acted through Wee1 and Cdr2. Cdr2 phosphorylation in vivo depended on Pom1, and Martin and Berthelot-Grosjean also found that Pom1 phosphorylated Cdr2 in vitro. During interphase, Cdr2 localizes to nodes in a medial cortical band; both groups found Cdr2-dependent nodal localization of Cdr1, with Moseley et al. demonstrating Cdr2-dependent nodal localization of Wee1 (and other proteins) as well. In the absence of Pom1, which forms a gradient starting from the cell tips, Cdr2 became mislocalized, and conditions with ectopic Pom1 activity (catalytically active Pom1 targeted to the cell middle or the Pom1 catalytic domain spread throughout the cortex) led to delayed entry into mitosis and increased cell length. Moreover, higher concentrations of Pom1 were apparent in the middles of short cells than in those of long cells. Both groups developed models in which the spatial gradient of Pom1 from the cell tips to the middle links cell length with mitosis. In this model, Pom1-dependent inhibition of Cdr2 relieves Cdr2 inhibition of Wee1, enabling Wee1-dependent phosphorylation of Cdk1 and thereby delaying mitosis in short cells; growth beyond a certain length limits exposure of Cdr2 to Pom1, releasing this inhibition and allowing mitosis to take place.
S. G. Martin, M. Berthelot-Grosjean, Polar gradients of the DYRK-family kinase Pom1 couple cell length with the cell cycle. Nature 459, 852–856 (2009). [PubMed]
J. B. Moseley, A. Mayeux, A. Paoletti, P. Nurse, A spatial gradient coordinates cell size and mitotic entry in fission yeast. Nature 459, 857–860 (2009). [PubMed]
K. E. Sawin, Cell division brought down to size. Nature 459, 782–783 (2009). [PubMed]