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A spatial gradient coordinates cell size and mitotic entry in fission yeast


Many eukaryotic cell types undergo size-dependent cell cycle transitions controlled by the ubiquitous cyclin-dependent kinase Cdk1 (refs 1–4). The proteins that control Cdk1 activity are well described but their links with mechanisms monitoring cell size remain elusive. In the fission yeast Schizosaccharomyces pombe, cells enter mitosis and divide at a defined and reproducible size owing to the regulated activity of Cdk1 (refs 2, 3). Here we show that the cell polarity protein kinase Pom1, which localizes to cell ends5, regulates a signalling network that contributes to the control of mitotic entry. This network is located at cortical nodes in the middle of interphase cells, and these nodes contain the Cdk1 inhibitor Wee1, the Wee1-inhibitory kinases Cdr1 (also known as Nim1) and Cdr2, and the anillin-like protein Mid1. Cdr2 establishes the hierarchical localization of other proteins in the nodes, and receives negative regulatory signals from Pom1. Pom1 forms a polar gradient extending from the cell ends towards the cell middle and acts as a dose-dependent inhibitor of mitotic entry, working through the Cdr2 pathway. As cells elongate, Pom1 levels decrease at the cell middle, leading to mitotic entry. We propose that the Pom1 polar gradient and the medial cortical nodes generate information about cell size and coordinate this with mitotic entry by regulating Cdk1 through Pom1, Cdr2, Cdr1 and Wee1.

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Figure 1: Interphase medial nodes contain multiple factors that physically interact.
Figure 2: Interphase nodes are organized by Cdr2 and contain Wee1.
Figure 3: Pom1 regulates Cdr2 and mitotic entry.
Figure 4: Pom1 levels at the cell centre control Cdr2-dependent entry into mitosis.

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We thank members of the Nurse laboratory for discussions and critical reading of the manuscript, A. Puszynska for technical assistance, The Rockefeller University Bio-Imaging Resource Center for assistance with microscopy, The Rockefeller University Proteomics Resource Center for mass spectrometry, K. Gould, J.-Q. Wu, T. Pollard, J. Bähler, F. Chang and K. Sawin for yeast strains, plasmids and antibodies, and S. Martin for sharing unpublished data and for discussions. J.B.M. was supported by a postdoctoral fellowship from the American Cancer Society (PF-07-129-01-MBC); A.P. by funding from ANR (BLAN06-3_135468), ARC (no. 4934) and FRM (INE20071110973); and P.N. by the Breast Cancer Research Foundation and The Rockefeller University.

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Correspondence to James B. Moseley.

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Moseley, J., Mayeux, A., Paoletti, A. et al. A spatial gradient coordinates cell size and mitotic entry in fission yeast. Nature 459, 857–860 (2009).

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