Open AccessWave patterns organize cellular protrusions and control cortical dynamics
Author(s) -
Miao Yuchuan,
Bhattacharya Sayak,
Banerjee Tatsat,
AbubakerSharif Bedri,
Long Yu,
Inoue Takanari,
Iglesias Pablo A,
Devreotes Peter N
Publication year - 2019
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20188585
Subject(s) - filopodia , pseudopodia , lamellipodium , biology , cytoskeleton , microbiology and biotechnology , actin , mechanism (biology) , positive feedback , regulator , signal transduction , neuroscience , biophysics , cell , physics , gene , genetics , engineering , quantum mechanics , electrical engineering
Cellular protrusions are typically considered as distinct structures associated with specific regulators. However, we found that these regulators coordinately localize as propagating cortical waves, suggesting a common underlying mechanism. These molecular events fell into two excitable networks, the signal transduction network STEN and the cytoskeletal network CEN with different wave substructures. Computational studies using a coupled‐network model reproduced these features and showed that the morphology and kinetics of the waves depended on strengths of feedback loops. Chemically induced dimerization at multiple nodes produced distinct, coordinated alterations in patterns of other network components. Taken together, these studies indicate: STEN positive feedback is mediated by mutual inhibition between Ras/Rap and PIP 2, while negative feedback depends on delayed PKB activation; PKB s link STEN to CEN ; CEN includes positive feedback between Rac and F‐actin, and exerts fast positive and slow negative feedbacks to STEN . The alterations produced protrusions resembling filopodia, ruffles, pseudopodia, or lamellipodia, suggesting that these structures arise from a common regulatory mechanism and that the overall state of the STEN ‐ CEN system determines cellular morphology.