Journal Article

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

Moseley, James B., Paoletti, Anne, Nurse, Paul, Mayeux, Adeline

2009

Overview

A time to divide Proliferating cells divide when they reach a certain size owing to regulated activity of cyclin-dependent kinase (Cdk1), but the links between Cdk1 regulators and mechanisms monitoring cell size have been elusive. Two papers in this issue describe how a fission yeast kinase Pom1, known to be a determinant of cell polarity, forms a polar gradient within the cell, which measures the length of the rod-shaped cells and induces cell division via negative regulation of the Cdk1 inhibitor Wee1. Cells normally grow to a certain size before they enter mitosis and divide, and entry into mitosis is known to be dependent on the activity of Cdk1; however, how this is sensed remains unknown. Here, and in an accompanying paper, it is shown that an intracellular polar gradient of dual-specificity the tyrosine-phosphorylation regulated kinase (DYRK) Pom1 relays size information to the Cdk1 inhibitor Wee1. 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 5 , 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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: antagonists & inhibitors / Biological and medical sciences / Brewer's yeast / CDC2 Protein Kinase / CDC2 Protein Kinase - antagonists & inhibitors / CDC2 Protein Kinase - metabolism / Cell Cycle Proteins / Cell Cycle Proteins - antagonists & inhibitors / Cell Cycle Proteins - metabolism / Cell cycle, cell proliferation / Cell division / Cell physiology / Cell Polarity / Cells / cytology / dimensions / enzyme inhibitors / Fundamental and applied biological sciences. Psychology / Genetic aspects / Humanities and Social Sciences / Interphase / letter / metabolism / Mitosis / Molecular and cellular biology / multidisciplinary / Nuclear fission / Nuclear Proteins / Nuclear Proteins - antagonists & inhibitors / Nuclear Proteins - metabolism / Phosphorylation / Physiological aspects / Protein kinases / Protein Kinases - metabolism / Protein Serine-Threonine Kinases / Protein Transport / Protein-Serine-Threonine Kinases - metabolism / Protein-Tyrosine Kinases / Protein-Tyrosine Kinases - antagonists & inhibitors / Protein-Tyrosine Kinases - metabolism / Schizosaccharomyces / Schizosaccharomyces - cytology / Schizosaccharomyces - metabolism / Schizosaccharomyces pombe / Schizosaccharomyces pombe Proteins / Schizosaccharomyces pombe Proteins - antagonists & inhibitors / Schizosaccharomyces pombe Proteins - metabolism / Science / Science (multidisciplinary) / Yeast / Yeasts