The core autophagy protein ATG5 controls the polarity of the Golgi apparatus and insulin secretion of pancreatic beta cells

作者全名："Pei, Xintong; Wang, Huiyu; Xu, Pingyong; Liang, Kuo; Yuan, Lin"

作者地址："[Pei, Xintong; Wang, Huiyu; Xu, Pingyong; Yuan, Lin] Chinese Acad Sci, Inst Biophys, Key Lab RNA Biol, Beijing 100101, Peoples R China; [Pei, Xintong; Xu, Pingyong] Univ Chinese Acad Sci, Coll Life Sci, Beijing 100101, Peoples R China; [Xu, Pingyong] Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China; [Xu, Pingyong] Chongqing Med Univ, Childrens Hosp, Dept Clin Lab, Chongqing 400014, Peoples R China; [Liang, Kuo] Capital Med Univ, XuanWu Hosp, Dept Gen Surg, Beijing, Peoples R China"

通信作者："Yuan, L (通讯作者)，Chinese Acad Sci, Inst Biophys, Key Lab RNA Biol, Beijing 100101, Peoples R China.; Liang, K (通讯作者)，Capital Med Univ, XuanWu Hosp, Dept Gen Surg, Beijing, Peoples R China."

来源：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000863300900005

JCR分区：Q2

影响因子：3.1

年份：2022

卷号：629

期号：　

开始页：26

结束页：33

文献类型：Article

关键词：Diabetes; Autophagy; Golgi apparatus; Polarity

摘要："Pancreatic beta cells are insulin-producing cells that are structurally and functionally polarized in the islets of Langerhans. The organization and position of the Golgi complex play a key role in maintaining a polarized cell state, but the factors and molecular mechanisms determining the Golgi polarization of pancreatic beta cells are still unknown. In the current study, using pancreatic beta cell-specific Atg5 knockout mice, we found that Atg5, an essential gene for autophagy, plays a pivotal role in regulating Golgi integrity and polarization by affecting the expression of genes involved in vesicle transport. Deletion of Atg5 led to endoplasmic reticulum (ER) stress and impaired the distribution of proinsulin and insulin secretion of pancreatic beta cells, which further exacerbates diabetes. These results contribute to a comprehensive understanding of autophagy-mediated Golgi polarization and its regulation of the function of pancreatic beta cells.(c) 2022 Elsevier Inc. All rights reserved."

基金机构："National Natural Science Foundation of China [31970704, 21927813, 32027901]; Strategic Priority Research Program of Chinese Academy of Sciences [XDB37040301]; Beijing Natural Science Foundation [7182063]"

基金资助正文："This project was supported by the National Natural Science Foundation of China (31970704, 21927813 and 32027901) , the Strategic Priority Research Program of Chinese Academy of Sciences (XDB37040301) and the Beijing Natural Science Foundation (7182063) . We thank Dr. Noboru Mizushima, Tokyo University and Dr. Weiping Zhang, Second Military Medical University for providing the mice harboring LoxP sites flanking exon 3 of the Atg5 gene and the mice expressing Cre recombinase under the control of Ins2 , respectively . We thank LetPub ( www.letpub.com ) for its lin- guistic assistance during the preparation of this manuscript."