RRC ID 54935
Author Fukushima S, Matsuoka S, Ueda M.
Title Excitable dynamics of Ras triggers spontaneous symmetry breaking of PIP3 signaling in motile cells.
Journal J Cell Sci
Abstract Spontaneous cell movement is underpinned by an asymmetric distribution of signaling molecules including small G proteins and phosphoinositides on the cell membrane. However, the molecular network necessary for spontaneous symmetry breaking has not been fully elucidated. Here, we report that, in Dictyostelium discoideum, the spatiotemporal dynamics of GTP bound Ras (Ras-GTP) breaks the symmetry due its intrinsic excitability even in the absence of extracellular spatial cues and downstream signaling activities. A stochastic excitation of local and transient Ras activation induced phosphatidylinositol (3,4,5)-trisphosphate (PIP3) accumulation via direct interaction with Phosphoinositide 3-kinase (PI3K), causing tightly coupled traveling waves that propagated along the membrane. Comprehensive phase analysis of the waves of Ras-GTP and PIP3 metabolism-related molecules revealed the network structure of the excitable system including positive-feedback regulation of Ras-GTP by the downstream PIP3. A mathematical model reconstituted a series of the observed symmetry-breaking phenomena, illustrating the essential involvement of Ras excitability in the cellular decision-making process.
Volume 132(5)
Published 2019-3-4
DOI 10.1242/jcs.224121
PII jcs.224121
PMID 30745337
PMC PMC6432713
MeSH Cell Membrane / metabolism* Cell Movement Cells, Cultured Dictyostelium / physiology* Feedback, Physiological Guanosine Triphosphate / metabolism Models, Theoretical Organisms, Genetically Modified Phosphatidylinositol 3-Kinases / genetics Phosphatidylinositol 3-Kinases / metabolism* Phosphatidylinositol Phosphates / metabolism Protein Transport Protozoan Proteins / genetics Protozoan Proteins / metabolism* Receptor Cross-Talk Signal Transduction ras Proteins / genetics ras Proteins / metabolism*
IF 4.517
Times Cited 8
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