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PLoS One

Title:		The coordination of cell growth during fission yeast mating requires Ras1-GTP hydrolysis
Author(s):		Weston C; Bond M; Croft W; Ladds G;
Address:		"Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Coventry, United Kingdom"
Journal Title:		PLoS One
Year:		2013
Volume:		20131016
Issue:		10
Page Number:		e77487 -
DOI:		10.1371/journal.pone.0077487
ISSN/ISBN:		1932-6203 (Electronic) 1932-6203 (Linking)
Abstract:		"The spatial and temporal control of polarity is fundamental to the survival of all organisms. Cells define their polarity using highly conserved mechanisms that frequently rely upon the action of small GTPases, such as Ras and Cdc42. Schizosaccharomyces pombe is an ideal system with which to study the control of cell polarity since it grows from defined tips using Cdc42-mediated actin remodeling. Here we have investigated the importance of Ras1-GTPase activity for the coordination of polarized cell growth during fission yeast mating. Following pheromone stimulation, Ras1 regulates both a MAPK cascade and the activity of Cdc42 to enable uni-directional cell growth towards a potential mating partner. Like all GTPases, when bound to GTP, Ras1 adopts an active conformation returning to an inactive state upon GTP-hydrolysis, a process accelerated through interaction with negative regulators such as GAPs. Here we show that, at low levels of pheromone stimulation, loss of negative regulation of Ras1 increases signal transduction via the MAPK cascade. However, at the higher concentrations observed during mating, hyperactive Ras1 mutations promote cell death. We demonstrate that these cells die due to their failure to coordinate active Cdc42 into a single growth zone resulting in disorganized actin deposition and unsustainable elongation from multiple tips. These results provide a striking demonstration that the deactivation stage of Ras signaling is fundamentally important in modulating cell polarity"
Keywords:		Actins/metabolism Guanosine Triphosphate/*metabolism Hydrolysis Pheromones/pharmacology Protein Binding/drug effects Schizosaccharomyces/*physiology Schizosaccharomyces pombe Proteins/*metabolism Signal Transduction/drug effects cdc42 GTP-Binding Protein/;
Notes:		"MedlineWeston, Cathryn Bond, Michael Croft, Wayne Ladds, Graham eng BB/G01227X/1/Biotechnology and Biological Sciences Research Council/United Kingdom Research Support, Non-U.S. Gov't 2013/10/23 PLoS One. 2013 Oct 16; 8(10):e77487. doi: 10.1371/journal.pone.0077487. eCollection 2013"