School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia.
Acta Biochim Biophys Sin (Shanghai). 2013 Jan;45(1):11-7. doi: 10.1093/abbs/gms095. Epub 2012 Nov 19.
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.
将低密度脂蛋白源性胆固醇(LDL-C)从内体隔室递送至质膜和内质网(ER)是一个重要但知之甚少的细胞过程。Niemann-Pick C1(NPC1)是晚期内体(LE)/溶酶体(Ly)的限制膜上的一种多跨整合膜蛋白,已知将腔内腔 LDL-C 插入 LE/Ly 的限制膜。最近的研究进展确定了调节 LDL-C 从 LE/Ly 中排出的新型细胞质蛋白,例如 ORP5,一种氧化固醇结合蛋白相关蛋白(ORPs)家族的成员,以及 Hrs/VPS27,一种成熟的内体分选复合物必需的运输途径调节剂。虽然 ORP5/ORPs 可作为细胞质胆固醇载体并以非囊泡方式输送胆固醇,但 Hrs/VPS27 如何调节内体胆固醇分选仍然是一个谜。我们讨论了 NPC1、Hrs 和 ORP5 之间的功能关系,并提出了 LDL-C 可能从内体隔室转移到其他细胞细胞器的可能方案。