A Model for Direction Sensing in Dictyostelium discoideum: Ras Activity and Symmetry Breaking Driven by a Gβγ-Mediated, Gα2-Ric8 -- Dependent Signal Transduction Network

摘要: Chemotaxis is a dynamic cellular process, comprised of direction sensing, polarization and locomotion, that leads to the directed movement eukaryotic cells along extracellular gradients. As primary step in response an individual cell spatial stimulus, sensing has attracted numerous theoretical treatments aimed at explaining experimental observations variety types. Here we propose new model based on experiments using Dictyostelium discoideum (Dicty). The built around reaction-diffusion-translocation system involves three main component processes: signal detection G-protein-coupled receptors (GPCR) for cyclic AMP (cAMP), transduction heterotrimetic G protein Gα2βγ, activation monomeric G-protein Ras. can predict experimentally-observed treated with latrunculin A, which removes feedback from downstream processes, under stimulus protocols. We show [Formula: see text] cycling modulated by Ric8, nonreceptor guanine exchange factor Dicty, drives multiple phases Ras amplification cAMP predicts both Gβγ are essential membrane-localized text], activated GTP-bearing form asymmetrical recruitment RasGEF while globally-diffusing mediates their activation. predicted level encodes sufficient 'memory' eliminate 'back-of-the wave' problem, effects diffusion shape also investigated. In contrast existing LEGI models chemotaxis, results do not require disparity between coefficients activator GEF inhibitor GAP. Since pathways study highly conserved Dicty mammalian leukocytes, serve as generic one sensing.