Exploration and stabilization of Ras1 mating zone: A mechanism with positive and negative feedbacks.

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State: Public
Version: Final published version
Serval ID
serval:BIB_E582BE1503B0
Type
Article: article from journal or magazin.
Collection
Publications
Title
Exploration and stabilization of Ras1 mating zone: A mechanism with positive and negative feedbacks.
Journal
PLoS computational biology
Author(s)
Khalili B., Merlini L., Vincenzetti V., Martin S.G., Vavylonis D.
ISSN
1553-7358 (Electronic)
ISSN-L
1553-734X
Publication state
Published
Issued date
07/2018
Peer-reviewed
Oui
Volume
14
Number
7
Pages
e1006317
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
In mating fission yeast cells, sensing and response to extracellular pheromone concentrations occurs through an exploratory Cdc42 patch that stochastically samples the cell cortex before stabilizing towards a mating partner. Active Ras1 (Ras1-GTP), an upstream regulator of Cdc42, and Gap1, the GTPase-activating protein for Ras1, localize at the patch. We developed a reaction-diffusion model of Ras1 patch appearance and disappearance with a positive feedback by a Guanine nucleotide Exchange Factor (GEF) and Gap1 inhibition. The model is based on new estimates of Ras1-GDP, Ras1-GTP and Gap1 diffusion coefficients and rates of cytoplasmic exchange studied by FRAP. The model reproduces exploratory patch behavior and lack of Ras1 patch in cells lacking Gap1. Transition to a stable patch can occur by change of Gap1 rates constants or local increase of the positive feedback rate constants. The model predicts that the patch size and number of patches depend on the strength of positive and negative feedbacks. Measurements of Ras1 patch size and number in cells overexpressing the Ras1 GEF or Gap1 are consistent with the model.
Keywords
Actins/metabolism, GTPase-Activating Proteins/metabolism, Guanine Nucleotide Exchange Factors/metabolism, Models, Biological, Pheromones/metabolism, Protein Binding, Reproduction, Schizosaccharomyces/enzymology, Schizosaccharomyces/metabolism, Schizosaccharomyces/physiology, Schizosaccharomyces pombe Proteins/metabolism, Signal Transduction, Stochastic Processes, cdc42 GTP-Binding Protein/metabolism, ras Proteins/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
31/07/2018 10:10
Last modification date
20/08/2019 16:08
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