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J Cell Biol

Title:		Inhibition of Ras activity coordinates cell fusion with cell-cell contact during yeast mating
Author(s):		Merlini L; Khalili B; Dudin O; Michon L; Vincenzetti V; Martin SG;
Address:		"Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland. Department of Physics, Lehigh University, Bethlehem, PA. Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland Sophie.Martin@unil.ch"
Journal Title:		J Cell Biol
Year:		2018
Volume:		20180216
Issue:		4
Page Number:		1467 - 1483
DOI:		10.1083/jcb.201708195
ISSN/ISBN:		1540-8140 (Electronic) 0021-9525 (Print) 0021-9525 (Linking)
Abstract:		"In the fission yeast Schizosaccharomyces pombe, pheromone signaling engages a signaling pathway composed of a G protein-coupled receptor, Ras, and a mitogen-activated protein kinase (MAPK) cascade that triggers sexual differentiation and gamete fusion. Cell-cell fusion requires local cell wall digestion, which relies on an initially dynamic actin fusion focus that becomes stabilized upon local enrichment of the signaling cascade on the structure. We constructed a live-reporter of active Ras1 (Ras1-guanosine triphosphate [GTP]) that shows Ras activity at polarity sites peaking on the fusion structure before fusion. Remarkably, constitutive Ras1 activation promoted fusion focus stabilization and fusion attempts irrespective of cell pairing, leading to cell lysis. Ras1 activity was restricted by the guanosine triphosphatase-activating protein Gap1, which was itself recruited to sites of Ras1-GTP and was essential to block untimely fusion attempts. We propose that negative feedback control of Ras activity restrains the MAPK signal and couples fusion with cell-cell engagement"
Keywords:		"Cell Polarity Enzyme Activation Feedback, Physiological GTPase-Activating Proteins/genetics/metabolism Gene Expression Regulation, Enzymologic Gene Expression Regulation, Fungal Kinetics Mitogen-Activated Protein Kinases/metabolism Saccharomyces cerevisia;"
Notes:		"MedlineMerlini, Laura Khalili, Bita Dudin, Omaya Michon, Laetitia Vincenzetti, Vincent Martin, Sophie G eng R01 GM098430/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Video-Audio Media 2018/02/18 J Cell Biol. 2018 Apr 2; 217(4):1467-1483. doi: 10.1083/jcb.201708195. Epub 2018 Feb 16"