Department of Pediatrics, Biochemistry and Molecular Biology, Atlantic Research Centre, Dalhousie University, Halifax, Nova Scotia, Canada.
Biochem J. 2010 Jul 1;429(1):13-24. doi: 10.1042/BJ20100263.
Cholesterol and its numerous oxygenated derivatives (oxysterols) profoundly affect the biophysical properties of membranes, and positively and negatively regulate sterol homoeostasis through interaction with effector proteins. As the bulk of cellular sterols are segregated from the sensory machinery that controls homoeostatic responses, an important regulatory step involves sterol transport or signalling between membrane compartments. Evidence for rapid, energy-independent transport between organelles has implicated transport proteins, such as the eukaryotic family of OSBP (oxysterol-binding protein)/ORPs (OSBP-related proteins). Since the founding member of this family was identified more than 25 years ago, accumulated evidence has implicated OSBP/ORPs in sterol signalling and/or sterol transport functions. However, recent evidence of sterol transfer activity by OSBP/ORPs suggests that other seemingly disparate functions could be the result of alterations in membrane sterol distribution or ancillary to this primary activity.
胆固醇及其众多氧化衍生物(氧化固醇)深刻影响膜的生物物理特性,并通过与效应蛋白相互作用,积极和消极地调节固醇稳态。由于细胞固醇的大部分与控制同型平衡反应的感应机制隔离开来,因此一个重要的调节步骤涉及固醇在膜隔室之间的运输或信号转导。有关细胞器之间快速、能量非依赖性运输的证据表明,固醇运输蛋白,如真核生物的 OSBP(氧化固醇结合蛋白)/ORPs(OSBP 相关蛋白)家族参与其中。自从该家族的创始成员在 25 年前被发现以来,越来越多的证据表明 OSBP/ORPs 参与固醇信号转导和/或固醇运输功能。然而,OSBP/ORPs 的固醇转移活性的最新证据表明,其他看似不同的功能可能是由于膜固醇分布的改变或辅助于这一主要活性的结果。