Mechanistic Insights into Membrane Protein Clustering Revealed by Visualizing EGFR Secretion

作     者：Haijiao Xu Jinrui Zhang Yijia Zhou Guanfang Zhao Mingjun Cai Jing Gao Lina Shao Yan Shi Hongru Li Hongbin Ji Yikai Zhao Hongda Wang 

作者机构：State Key Laboratory of Electroanalytical ChemistryChangchun Institute of Applied ChemistryChinese Academy of SciencesChangchun130022 JilinChina State Key Laboratory of Cell BiologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China School of Life Science and TechnologyShanghaiTech UniversityShanghai 200031China University of Science and Technology of ChinaHefei230026 AnhuiChina University of Chinese Academy of SciencesBeijing 100049China School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 130102China Laboratory for Marine Biology and BiotechnologyQingdao National Laboratory for Marine Science and TechnologyQingdao266237 ShandongChina 

出 版 物：《Research》 (研究（英文）)

年 卷 期：2023年第2022卷第1期

页      面：353-366页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 071006[理学-神经生物学] 

基　　金：supported by the National Natural Science Foundation of China(nos.22150003,21727816 and 21721003) the Scientific Instrument Developing Project of the Chinese Academy of Sciences(ZDKYYQ20220005) the Foundation of Science and Technology Department of Jilin Province(YDZJ202201ZYTS530) 

主　　题：distribution EGFR eventually 

摘      要：Most plasmalemmal proteins are organized into clusters to modulate various cellular ***,the machineries that regulate protein clustering remain largely ***,with EGFR as an example,we directly and in detail visualized the entire process of EGFR from synthesis to secretion onto the plasma membrane(PM)using a high-speed,high-resolution spinning-disk confocal ***,colocalization imaging revealed that EGFR secretory vesicles underwent transport from the ER to the Golgi to the PM,eventually forming different distribution forms on the apical and basal membranes;that is,most EGFR formed larger clusters on the apical membrane than the basal membrane.A dynamic tracking image and further siRNA interference experiment confirmed that fusion of secretory vesicles with the plasma membrane led to EGFR clusters,and we showed that EGFR PM clustering may be intimately related to EGFR signaling and cell ***,we found that the size and origin of the secretory vesicles themselves may determine the difference in the distribution patterns of EGFR on the *** importantly,we showed that actin influenced the EGFR distribution by controlling the fusion of secretory vesicles with the ***,a comprehensive understanding of the EGFR secretion process helps us to unravel the EGFR clustering process and elucidate the key factors determining the differences in the spatial distribution of EGFR PM,highlighting the correlation between EGFR secretion and its PM distribution pattern.