SSBD:database

Detail of Fig2_EGF30nM_60s

Michio Hiroshima, Chan-Gi Pack, Kazunari Kaizu, Koichi Takahashi, Masahiro Ueda, Yasushi Sako (2018) Transient Acceleration of Epidermal Growth Factor Receptor Dynamics Produces Higher-Order Signaling Clusters., Journal of molecular biology, Volume 430, Number 9, pp. 1386-1401

Published in 2018 Apr 27 (Electronic publication in March 2, 2018, midnight )

• doi: 10.1016/j.jmb.2018.02.018
• pmid: 29505756
  

(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.

• Animals
• CHO Cells
• Cluster Analysis
• Cricetulus
• Cytoplasm/metabolism
• Epidermal Growth Factor/metabolism[major]
• ErbB Receptors/chemistry
• ErbB Receptors/metabolism
• Fluorescent Antibody Technique
• GRB2 Adaptor Protein/metabolism[major]
• Humans
• Signal Transduction
• Single Molecule Imaging/methods[major]
• Spatio-Temporal Analysis