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A systems approach to investigate GPCR-mediated Ras signaling network in chemoattractant sensing.

A systems approach to investigate GPCR-mediated Ras signaling network in chemoattractant sensing.

Authors :
Xu X
Quan W
Zhang F
Jin T
Source :
Molecular biology of the cell [Mol Biol Cell] 2022 Mar 01; Vol. 33 (3), pp. ar23. Date of Electronic Publication: 2021 Dec 15.
Publication Year :
2022

Abstract

A GPCR-mediated signaling network enables a chemotactic cell to generate adaptative Ras signaling in response to a large range of concentrations of a chemoattractant. To explore potential regulatory mechanisms of GPCR-controlled Ras signaling in chemosensing, we applied a software package, Simmune, to construct detailed spatiotemporal models simulating responses of the cAR1-mediated Ras signaling network. We first determined the dynamics of G-protein activation and Ras signaling in Dictyostelium cells in response to cAMP stimulations using live-cell imaging and then constructed computation models by incorporating potential mechanisms. Using simulations, we validated the dynamics of signaling events and predicted the dynamic profiles of those events in the cAR1-mediated Ras signaling networks with defective Ras inhibitory mechanisms, such as without RasGAP, with RasGAP overexpression, or with RasGAP hyperactivation. We describe a method of using Simmune to construct spatiotemporal models of a signaling network and run computational simulations without writing mathematical equations. This approach will help biologists to develop and analyze computational models that parallel live-cell experiments.

Details

Language :
English
ISSN :
1939-4586
Volume :
33
Issue :
3
Database :
MEDLINE
Journal :
Molecular biology of the cell
Publication Type :
Academic Journal
Accession number :
34910560
Full Text :
https://doi.org/10.1091/mbc.E20-08-0545