Comparison of class B scavenger receptors, CD36 and scavenger receptor BI (SR-BI), shows that both receptors mediate high density lipoprotein-cholesteryl ester selective uptake but SR-BI exhibits a unique enhancement of cholesteryl ester uptake
Comparison of class B scavenger receptors, CD36 and scavenger receptor BI (SR-BI), shows that both receptors mediate high density lipoprotein-cholesteryl ester selective uptake but SR-BI exhibits a unique enhancement of cholesteryl ester uptake
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DOI：
10.1074/jbc.274.1.41
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发表时间：
1999-01-01
影响因子：
4.8
通讯作者：
Williams, DL
中科院分区：
文献类型：
--
作者：
Connelly, MA;Klein, SM;Williams, DL
清道夫受体BI(SR-BI)介导高密度脂蛋白(高密度脂蛋白)胆固醇酯(CE)的选择性摄取，这一过程使高密度脂蛋白(HDLCE)进入细胞，而不会内化和降解高密度脂蛋白(HDL)颗粒。SR-BI介导HDLCE选择性摄取的生化机制尚不清楚。鉴于CE会在一定程度上从高密度脂蛋白转移到无蛋白质的合成膜，一种假设是SR-BI的作用主要是将高密度脂蛋白拴在靠近细胞表面的地方，以促进CE从颗粒到质膜的转移。在本研究中，通过比较小鼠SR-BI(MSR-BI)和大鼠CD36(RCD36)(一种密切相关的B类清道夫受体)介导的HDLCE选择性摄取来验证这一假说。MSR-BI和rCD36均以高亲和力结合高密度脂蛋白，两种受体均介导高密度脂蛋白选择性摄取。然而，SR-BI介导高密度脂蛋白CE选择性摄取的效率是rCD36的7倍，rCD36介导的高密度脂蛋白CE选择性摄取依赖于高密度脂蛋白与受体的结合，因为阻止高密度脂蛋白结合的突变也阻止了高密度脂蛋白CE的选择性摄取。这些数据使我们假设，高密度脂蛋白CE选择性摄取的一个组成部分是高密度脂蛋白颗粒与细胞表面的连接。为了探索导致MSR-BI选择性摄取效率更高的分子结构域，我们比较了MSR-BI、清道夫受体BII以及由MSR-BI和rCD36形成的各种嵌合受体之间的结合和选择性摄取。结果表明，MSR-BI的胞外结构域对于高密度脂蛋白CE的有效摄取是必不可少的，但C端的胞质尾巴对选择性摄取过程也有重要影响。
Scavenger receptor BI (SR-BI) mediates the selective uptake of high density lipoprotein (HDL) cholesteryl ester (CE), a process by which HDL CE is taken into the cell without internalization and degradation of the HDL particle. The biochemical mechanism by which SR-BI mediates the selective uptake of HDL CE is poorly understood. Given that CE transfer will occur to some extent from HDL to protein-free synthetic membranes, one hypothesis is that the role of SR-BI is primarily to tether HDL close to the cell surface to facilitate CE transfer from the particle to the plasma membrane. In the present study, this hypothesis was tested by comparing the selective uptake of HDL CE mediated by mouse SR-BI (mSR-BI) with that mediated by rat CD36 (rCD36), a closely related class B scavenger receptor. Both mSR-BI and rCD36 bind HDL with high affinity, and both receptors mediate HDL CE selective uptake. However, SR-BI mediates selective uptake of HDL CE with a 7-fold greater efficiency than rCD36, HDL CE selective uptake mediated by rCD36 is dependent on HDL binding to the receptor, since a mutation that blocks HDL binding also blocks HDL CE selective uptake. These data lead us to hypothesize that one component of HDL CE selective uptake is the tethering of HDL particles to the cell surface. To explore the molecular domains responsible for the greater efficiency of selective uptake by mSR-BI, we compared binding and selective uptake among mSR-BI, scavenger receptor BII, and various chimeric receptors formed from mSR-BI and rCD36. The results show that the extracellular domain of mSR-BI is essential for efficient HDL CE uptake, but the C-terminal cytoplasmic tail also has a major influence on the selective uptake process.