https://scholars.lib.ntu.edu.tw/handle/123456789/641494
標題: | Endosomal Arl4A attenuates EGFR degradation by binding to the ESCRT-II component VPS36 | 作者: | Lin, Shin-Jin Lin, Ming-Chieh Liu, Tsai-Jung Tsai, Yueh-Tso Tsai, Ming-Ting FANG-JEN LEE |
公開日期: | 29-十一月-2023 | 出版社: | Nature Research | 卷: | 14 | 期: | 1 | 來源出版物: | Nature Communications | 摘要: | Ligand-induced epidermal growth factor receptor (EGFR) endocytosis followed by endosomal EGFR signaling and lysosomal degradation plays important roles in controlling multiple biological processes. ADP-ribosylation factor (Arf)-like protein 4 A (Arl4A) functions at the plasma membrane to mediate cytoskeletal remodeling and cell migration, whereas its localization at endosomal compartments remains functionally unknown. Here, we report that Arl4A attenuates EGFR degradation by binding to the endosomal sorting complex required for transport (ESCRT)-II component VPS36. Arl4A plays a role in prolonging the duration of EGFR ubiquitinylation and deterring endocytosed EGFR transport from endosomes to lysosomes under EGF stimulation. Mechanistically, the Arl4A-VPS36 direct interaction stabilizes VPS36 and ESCRT-III association, affecting subsequent recruitment of deubiquitinating-enzyme USP8 by CHMP2A. Impaired Arl4A-VPS36 interaction enhances EGFR degradation and clearance of EGFR ubiquitinylation. Together, we discover that Arl4A negatively regulates EGFR degradation by binding to VPS36 and attenuating ESCRT-mediated late endosomal EGFR sorting. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/641494 | ISSN: | 2041-1723 | DOI: | 10.1038/s41467-023-42979-9 |
顯示於: | 分子醫學研究所 |
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