RRC ID 53822
Author Hiroshima M, Pack CG, Kaizu K, Takahashi K, Ueda M, Sako Y.
Title Transient Acceleration of Epidermal Growth Factor Receptor Dynamics Produces Higher-Order Signaling Clusters.
Journal J Mol Biol
Abstract Cell signaling depends on spatiotemporally regulated molecular interactions. Although the movements of signaling proteins have been analyzed with various technologies, how spatial dynamics influence the molecular interactions that transduce signals is unclear. Here, we developed a single-molecule method to analyze the spatiotemporal coupling between motility, clustering, and signaling. The analysis was performed with the epidermal growth factor receptor (EGFR), which triggers signaling through its dimerization and phosphorylation after association with EGF. Our results show that the few EGFRs isolated in membrane subdomains were released by an EGF-dependent increase in their diffusion area, facilitating molecular associations and producing immobile clusters. Using a two-color single-molecule analysis, we found that the EGF-induced state transition alters the properties of the immobile clusters, allowing them to interact for extended periods with the cytoplasmic protein, GRB2. Our study reveals a novel correlation between this molecular interaction and its mesoscale dynamics, providing the initial signaling node.
Volume 430(9)
Pages 1386-1401
Published 2018-4-27
DOI 10.1016/j.jmb.2018.02.018
PII S0022-2836(18)30091-3
PMID 29505756
MeSH Animals CHO Cells Cluster Analysis Cricetulus Cytoplasm / metabolism Epidermal Growth Factor / metabolism* ErbB Receptors / chemistry ErbB Receptors / metabolism Fluorescent Antibody Technique GRB2 Adaptor Protein / metabolism* Humans Signal Transduction Single Molecule Imaging / methods* Spatio-Temporal Analysis
IF 4.894
Times Cited 6
DNA material EGFR-EGFP (RDB15996)
Human and Animal Cells CHO-K1(RCB0285)