C型尼曼-匹克蛋白1和2在细胞内脂质平衡中的作用

Niemann-pick protein C1(NPC1) is a large integral membrane glycoprotein that resides in late endosomes,whereas niemann-pick protein C2(NPC2) is a small soluble protein found in the lumen of lysosomes.NPC1 protein is believed to facilitate the transport of lipids,particularly cholesterol,from late endosomes/lysosomes to the Golgi apparatus,endoplasmic reticulum and plasma membrane.NPC2 primarily plays a role in the egress of cholesterol and glycolipids from lysosomes.Mutations in either NPC1 or NPC2 result in aberrant lipid transport from endocytic compartments,which results in lysosomal storage of a complex mixture of lipids,primarily cholesterol and glycosphingolipids.The NPC proteins regulate sterol homeostasis through production of LDL cholesterol-derived oxysterols.Oxysterols are endogenous ligands for the liver X receptors(LXRs),which can upregulate ATP binding cassette transporter A1(ABCA1) expression.ABCA1 may have antiatherogenic effects through the efflux of it-mediated cholesterol.Meanwhile,NPC1 heterozygote mutation confers substantial resistance to lesional necrosis and lesional macrophage apoptosis.Study of the NPC proteins will help us for further understanding of the mechanisms involved in atherogenesis.