Journal
JOURNAL OF CELL SCIENCE
Volume 132, Issue 5, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.224121
Keywords
Cell signaling; Ras GTPase; Phosphatidylinositol lipid; Excitable system; Self-organization; Spontaneous migration
Categories
Funding
- AMED-CREST Japan Agency for Medical Research and Development grant [JP17gm0910001]
- Japan Society for the Promotion of Science (JSPS) [17J02075]
- Grants-in-Aid for Scientific Research [17J02075] Funding Source: KAKEN
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available