膽固醇是動(dòng)物細(xì)胞膜的重要組成部分,其濃度受轉(zhuǎn)錄水平和轉(zhuǎn)錄后水平上的反饋系統(tǒng)緊密調(diào)節(jié).本文主要討論這一領(lǐng)域的最新進(jìn)展來解釋細(xì)胞利用一種膜鑲嵌蛋白監(jiān)控固醇的濃度并對其體內(nèi)合成和攝取的機(jī)制!
簡述
在已知的動(dòng)物細(xì)胞反饋調(diào)節(jié)系統(tǒng)中,膽固醇調(diào)節(jié)系統(tǒng)是唯一一種調(diào)節(jié)作用物膽固醇的合成降解完全在細(xì)胞質(zhì)膜中進(jìn)行的的一種系統(tǒng).細(xì)胞中監(jiān)控膜固醇水平采用了內(nèi)質(zhì)網(wǎng)上的兩種膜鑲嵌蛋白--Scap和3-羥基-3-甲基谷胺酰輔酶A還原酶(3-hydroxyl-3-methylglutaryl coenzyme A reductase HMG CoA Reductase).這些蛋白有一個(gè)共同的內(nèi)膜序列叫做固醇感應(yīng)域.通過這個(gè)結(jié)構(gòu)域,固醇促進(jìn)Scap和HMG-CoA還原酶與Insigs的結(jié)合,一種新發(fā)現(xiàn)確定其結(jié)構(gòu)的內(nèi)質(zhì)網(wǎng)膜蛋白.Scap和HMG-CoA還原酶結(jié)合在Insig上使其構(gòu)象發(fā)生變化,發(fā)揮作用限制膽固醇的合成.通過調(diào)控Scap和HMG-CoA還原酶,Insigs占據(jù)了轉(zhuǎn)錄和后轉(zhuǎn)錄水平調(diào)控信號通路調(diào)節(jié)下的的維系膽固醇的體液穩(wěn)態(tài)過程中重要的轉(zhuǎn)折點(diǎn)!
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.
（翻譯：中國生命科學(xué)論壇會(huì)員 rafael.cau）
