期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 430, 期 9, 页码 1386-1401出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2018.02.018
关键词
cell signaling regulation; membrane subdomain; receptor tyrosine kinase; single-molecule tracking; molecular mobility and clustering
资金
- Grants-in-Aid for Scientific Research [15H02394, 15KT0087, 17H06021, 16H00788] Funding Source: KAKEN
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. (C) 2018 Elsevier Ltd. All rights reserved.
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