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Abstract
Cell polarity is essential for various cellular functions during both proliferative and developmental stages, and it displays dynamic alterations in response to intracellular and extracellular cues. However, the molecular mechanisms underlying spatiotemporal control of polarity transition are poorly understood. Here, we show that fission yeast Cki3 (a casein kinase 1γ homolog) is a critical regulator to ensure persistent monopolar growth during S phase. Unlike the wild type, cki3 mutant cells undergo bipolar growth when S phase is blocked, a condition known to delay transition from monopolar to bipolar growth (termed NETO [new end takeoff]). Consistent with this role, Cki3 kinase activity is substantially increased, and cells lose their viability in the absence of Cki3 upon an S-phase block. Cki3 acts downstream of the checkpoint kinase Cds1/Chk2 and calcineurin, and the latter physically interacts with Cki3. Autophosphorylation in the C terminus is inhibitory toward Cki3 kinase activity, and calcineurin is responsible for its dephosphorylation. Cki3 localizes to the plasma membrane, and this localization requires the palmitoyltransferase complex Erf2-Erf4. Membrane localization is needed not only for proper NETO timing but also for Cki3 kinase activity. We propose that Cki3 acts as a critical inhibitor of cell polarity transition under S-phase arrest.
Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.01465-14.
ACKNOWLEDGMENTS
We thank Mohan Balasubramanian for his generous gift of the set of kinase deletions and Eiji Kinoshita for Phos-tag.
T.K. was the recipient of a JSPS fellowship (DC1; PD) and was partly supported by the Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation from JSPS. This work was supported by Cancer Research UK (T.T.) and the Ministry of Education, Culture, Sports, Science and Technology (D.H. and K.K.).
The experiments were designed by T.K., K.K., D.H., and T.T. T.K. performed the majority of the experiments and data analysis. K.K. and M.K. performed mutant screening. S.G.M. and Y.O. provided materials and made critical suggestions during the course of this work. T.K. and T.T. wrote the paper with suggestions from the other authors.