A new regulator of autophagy initiation in glia

doi:10.1080/15548627.2023.2251821

	A new regulator of autophagy initiation in glia
	Wang, Linfang1,2 ; Zhang, Shiping1 ; Yi, Shuanglong1,2 ; Ho, Margaret S.1,3
	2023-08-29
发表期刊	AUTOPHAGY (IF:14.6[JCR-2023],16.8[5-Year])
ISSN	1554-8627
EISSN	1554-8635
发表状态	已发表
DOI	10.1080/15548627.2023.2251821
摘要	Macroautophagy/autophagy is the major degradation pathway in neurons for eliminating damaged proteins and organelles in Parkinson disease (PD). Like neurons, glial cells are important contributors to PD, yet how autophagy is executed in glia and whether it is using similar interplay as in neurons or other tissues, remain largely elusive. Recently, we reported that the PD risk factor, GAK/aux (cyclin-G-associated kinase/auxilin), regulates the onset of glial autophagy. In the absence of GAK/aux, the number and size of the autophagosomes and autophagosomal precursors increase in adult fly glia and mouse microglia. The protein levels of components in the initiation and class III phosphatidylinositol 3-kinase (PtdIns3K) complexes are generally upregulated. GAK/aux interacts with the master initiation regulator ULK1/Atg1 (unc-51 like autophagy activating kinase 1) via its uncoating domain, hinders autophagy activation by competing with ATG13 (autophagy related 13) for binding to the ULK1 C terminus, and regulates ULK1 trafficking to phagophores. Nonetheless, lack of GAK/aux impairs the autophagic flux and blocks substrate degradation, suggesting that GAK/aux might play additional roles. Overall, our findings reveal a new regulator of autophagy initiation in glia, advancing our understanding on how glia contribute to PD in terms of eliminating pathological protein aggregates.Abbreviations: ATG13: autophagy related 13; GAK/aux: cyclin G associated kinase/auxilin; PtdIns3K: phosphatidylinositol 3-kinase; PD: Parkinson disease; ULK1/Atg1: unc-51 like autophagy activating kinase 1.
关键词	Glia autophagy Gak/Aux Ulk1/Atg1 autophagy initiation Parkinson's disease
URL	查看原文
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China[32170962]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:001064804600001
出版者	TAYLOR & FRANCIS INC
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/331103
专题	生命科学与技术学院生命科学与技术学院_PI研究组_何淑君组生命科学与技术学院_博士生
通讯作者	Ho, Margaret S.
作者单位	1.ShanghaiTech Univ, Pudong New Area, Sch Life Sci & Technol, Shanghai, Peoples R China 2.Univ Chinese Acad Sci, Coll Life Sci, Beijing, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, Pudong New Area, Shanghai 201210, Peoples R China
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
第一作者的第一单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Wang, Linfang,Zhang, Shiping,Yi, Shuanglong,et al. A new regulator of autophagy initiation in glia[J]. AUTOPHAGY,2023.
APA	Wang, Linfang,Zhang, Shiping,Yi, Shuanglong,&Ho, Margaret S..(2023).A new regulator of autophagy initiation in glia.AUTOPHAGY.
MLA	Wang, Linfang,et al."A new regulator of autophagy initiation in glia".AUTOPHAGY (2023).