胆固醇是动物细胞膜的重要组成部分,其浓度受转录水平和转录后水平上的反馈系统紧密调节.本文主要讨论这一领域的最新进展来解释细胞利用一种膜镶嵌蛋白监控固醇的浓度并对其体内合成和摄取的机制!
简述
在已知的动物细胞反馈调节系统中,胆固醇调节系统是唯一一种调节作用物胆固醇的合成降解完全在细胞质膜中进行的的一种系统.细胞中监控膜固醇水平采用了内质网上的两种膜镶嵌蛋白--Scap和3-羟基-3-甲基谷胺酰辅酶A还原酶(3-hydroxyl-3-methylglutaryl coenzyme A reductase HMG CoA Reductase).这些蛋白有一个共同的内膜序列叫做固醇感应域.通过这个结构域,固醇促进Scap和HMG-CoA还原酶与Insigs的结合,一种新发现确定其结构的内质网膜蛋白.Scap和HMG-CoA还原酶结合在Insig上使其构象发生变化,发挥作用限制胆固醇的合成.通过调控Scap和HMG-CoA还原酶,Insigs占据了转录和后转录水平调控信号通路调节下的的维系胆固醇的体液稳态过程中重要的转折点!
原文:
Protein Sensors for Membrane Sterols
Joseph L.Goldstein,Russell A.DeBose-Boyed,and Michael S.Brown
Department of Molecular Genetics,University of Texas Southwestern Medical Center,Dallas,Texas 75390,USA
DOI 10.1016/j.cell 2005 12.022
Cholesterol is an essential component of animal cell membranes,and its concentration is tightly controlled by a feedback system that operates at transcriptional and posttranscriptional levels.Here,we discuss recent advances that explain how cells employ an ensemble of membrane-embedded proteins to monitor sterol concentration and adjust sterol synthesis and uptake.
Introduction
Among the known feedback control systems in animal cells,the cholesterol sysyem is unique in that the regulated end-product--cholesterol is sequenstered entirely within cell membranes.To monitor levels of membrane sterols,cells employ two membrane-embedded proteins of the endoplasmic reticulum(ER)--Scap and HMG-CoA Reductase(3-hydroxyl-3-methylglutamyl CoA Reductase).These proteins share a polytopic inframembrane sequence called the sterol sensing domain.Through this domain,sterols cause Scap and HMG-CoA Ruductase to bind to Insigs,newly characterized membrane proteins of the ER.Upon binding Scap and reductase,Insigs exert actions that limit cholesterol synthesis.By controlling Scap and reductase,and posttranscriptional regulatary mechanisms that assure cholesterol homoestasis.
(翻译:中国生命科学论坛会员 rafael.cau)