2024/10/09 by Mitsuhiro Abe, Masataka Yanagawa, Michio Hiroshima +2 · 1 voice
Biochemistry, Genetics and Molecular Biology · #Advanced Electron Microscopy Techniques and Applications #Advanced Fluorescence Microscopy Techniques #Heat shock proteins research
paper · doi:10.7554/elife.101652
openalex publication_date 2024/10/09 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/13
Anionic lipid molecules, including phosphatidylinositol-4,5-bisphosphate (PI(4,5)P 2 ), are implicated in the regulation of epidermal growth factor receptor (EGFR). However, the role of the spatiotemporal dynamics of PI(4,5)P 2 in the regulation of EGFR activity in living cells is not fully understood, as it is difficult to visualize the local lipid domains around EGFR. Here, we visualized both EGFR and PI(4,5)P 2 nanodomains in the plasma membrane of HeLa cells using super-resolution single-molecule microscopy. The EGFR and PI(4,5)P 2 nanodomains aggregated before stimulation with epidermal growth factor (EGF) through transient visits of EGFR to the PI(4,5)P 2 nanodomains. The degree of coaggregation decreased after EGF stimulation and depended on phospholipase Cγ, the EGFR effector hydrolyzing PI(4,5)P 2 . Artificial reduction in the PI(4,5)P 2 content of the plasma membrane reduced both the dimerization and autophosphorylation of EGFR after stimulation with EGF. Inhibition of PI(4,5)P 2 hydrolysis after EGF stimulation decreased phosphorylation of EGFR-Thr654. Thus, EGFR kinase activity and the density of PI(4,5)P 2 around EGFR molecules were found to be mutually regulated.