Surf4,cargo trafficking,lipid metabolism,and therapeutic implications  

作　　者：Yishi Shen Hong-Mei Gu Shucun Qin Da-Wei Zhang 

机构地区：[1]Group on the Molecular and Cell Biology of Lipids and Department of Pediatrics,Faculty of Medicine and Dentistry,University of Alberta,Edmonton ABT6R2G3,Canada [2]Institute of Atherosclerosis in Shandong First Medical University(Shandong Academy of Medical Sciences),Taian 271016,China

出　　处：《Journal of Molecular Cell Biology》2022年第9期3-13,共11页分子细胞生物学报（英文版）

基　　金：This work was supported by grants from Canadian Institutes of Health Research(PS 178091);the National Natural Science Foundation of China(NSFC 81929002);D.-W.Z.was also supported by grants from the Natural Sciences and Engineering Research Council of Canada(RGPIN-2016-06479);Canadian Institutes of Health Research(PS 155994);S.Q.was supported by 91539114,ts201511057,and Academic Promotion Program of Shandong First Medical University(2019QL010 and 2019PT009);Y.S.was partly supported by Motyl Graduate Studentships in Cardiac Sciences from the Faculty of Medicine and Dentistry at the University of Alberta.

摘　　要：Surfeit 4 is a polytopic transmembrane protein that primarily resides in the endoplasmic reticulum(ER)membrane.It is ubiquitously expressed and functions as a cargo receptor,mediating cargo transport from the ER to the Golgi apparatus via the canonical coat protein complex Il(CoPll)-coated vesicles or specific vesicles.It also participates in ER-Golgi protein trafficking through a tubular network.Meanwhile,it facilitates retrograde transportation of cargos from the Golgi apparatus to the ER through Coplcoated vesicles.Surf4 can selectively mediate export of diverse cargos,such as PCSK9 very low-density lipoprotein(VLDL),progranulin,α1-antitrypsin,STING,proinsulin,and erythropoietin.It has been implicated in facilitating VLDL secretion,promoting cell proliferation and migration,and increasing replication of positive-strand RNA viruses.Therefore,Surf4 plays a crucial role in various physiological and pathophysiological processes and emerges as a promising therapeutic target.However,the molecular mechanisms by which Surf4 selectively sorts diverse cargos for ER-Golgi protein trafficking remain elusive.Here,we summarize the most recent advances in Surf4,focusing on its role in lipid metabolism.

关 键 词：VLDL secretion cargo receptor PCSK9 lipid metabolism atherosclerosis TRAFFICKING 

分 类 号：R541.4[医药卫生—心血管疾病]