title: A spatial gradient coordinates cell size and mitotic entry in fission yeast.
abstract: 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 ends, 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.
authors.affiliation: The Rockefeller University, New York, New York 10065, USA. jmoseley@rockefeller.edu
authors.forename: James B
authors.initials: JB
authors.lastname: Moseley
authors.forename: Adeline
authors.initials: A
authors.lastname: Mayeux
authors.forename: Anne
authors.initials: A
authors.lastname: Paoletti
authors.forename: Paul
authors.initials: P
authors.lastname: Nurse
mesh_terms: D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D016764:Cell Polarity; D007399:Interphase; D008938:Mitosis; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology* / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C489694:Mid1 protein, S pombe; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; D011494:Protein Kinases; C112212:Pom1 protein, S pombe; C080364:cdr1 protein, S pombe; C068689:wee1 protein, S pombe; D011505:Protein-Tyrosine Kinases; C542567:Cdr2 protein, S pombe; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase