Endosomal cholesterol trafficking: protein factors at a glance

被引:19
作者
Du, Ximing [1 ]
Yang, Hongyuan [1 ]
机构
[1] Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW 2052, Australia
基金
澳大利亚研究理事会; 英国医学研究理事会;
关键词
NPC1; NPC2; OSBP/ORP; Hrs; endosomal cholesterol transport; OXYSTEROL-BINDING PROTEIN; PICK C1 PROTEIN; PURIFIED NPC1 PROTEIN; STEROL-SENSING DOMAIN; HMG-COA REDUCTASE; MEMBRANE-PROTEIN; 3-HYDROXY-3-METHYLGLUTARYL-COA REDUCTASE; LIPID-BILAYERS; C2; PROTEIN; TRANSPORT;
D O I
10.1093/abbs/gms095
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The delivery of low-density lipoprotein-derived cholesterol (LDL-C) from endosomal compartments to the plasma membrane and the endoplasmic reticulum (ER) is an important yet poorly understood cellular process. Niemann-Pick C1 (NPC1), a multi-pass integral membrane protein on the limiting membranes of late endosomes (LE)/lysosomes (Ly), is known to insert lumenal LDL-C to the limiting membrane of LE/Ly. Recent progress has identified novel cytoplasmic proteins that regulate the exit of LDL-C from LE/Ly, such as ORP5, a member of the oxysterol-binding protein-related protein (ORPs) family, and Hrs/VPS27, a well-established regulator of the endosomal sorting complex required for transport pathway. Whereas ORP5/ORPs may serve as cytosolic cholesterol carriers and deliver cholesterol in a non-vesicular manner, how Hrs/VPS27 regulate endosomal cholesterol sorting remains enigmatic. We discuss the functional relationship between NPC1, Hrs, and ORP5, and formulate possible schemes on how LDL-C may be moved from endosomal compartments to other cellular organelles.
引用
收藏
页码:11 / 17
页数:7
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