Caveolin, Sterol Carrier Protein-2, Membrane Cholesterol-Rich Microdomains and Intracellular Cholesterol Trafficking

Caveolin, Sterol Carrier Protein-2, Membrane Cholesterol-Rich Microdomains and Intracellular Cholesterol Trafficking
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DOI:
10.1007/978-90-481-8622-8_10
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发表时间:
2010-01-01
期刊:
CHOLESTEROL BINDING AND CHOLESTEROL TRANSPORT PROTEINS: STRUCTURE AND FUNCTION IN HEALTH AND DISEASE
影响因子:
--
通讯作者:
Kier, Ann B.
Kier, Ann B.
中科院分区:
其他
文献类型:
--
作者:
Schroeder, Friedhelm;Huang, Huan;Kier, Ann B.

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虽然膜侧面微结构域的存在已为人所知 30 多年,但由于发现富含胆固醇的微结构域具有重要的生物学功能,因此在过去十年中人们对这些结构的兴趣加速增长。人们越来越认识到,真核细胞质膜中富含胆固醇的微结构域代表了参与跨膜营养吸收(胆固醇、脂肪酸、葡萄糖等)、细胞信号传导、免疫识别、病原体进入和许多其他作用的多种细胞蛋白的组织联系。然而,尽管取得了这些进展,但人们对这些质膜微区中胆固醇本身的组织知之甚少。尽管多种非甾醇标记表明活细胞质膜中存在微结构域,但这些研究都没有证明活细胞的这些微结构域中富含胆固醇。此外,富含胆固醇的膜微结构域作为细胞内胆固醇运输蛋白(例如甾醇载体蛋白-2 (SCP-2))的靶标的作用才刚刚开始被理解,这些蛋白促进胆固醇摄取和跨细胞运输以靶向储存(胆固醇酯)或流出。在此,我们总结了该领域的背景以及最近取得的进展,这些进展增进了我们对这些问题的理解。
While the existence of membrane lateral microdomains has been known for over 30 years, interest in these structures accelerated in the past decade due to the discovery that cholesterol-rich microdomains serve important biological functions. It is increasingly appreciated that cholesterol-rich microdomains in the plasma membranes of eukaryotic cells represent an organizing nexus for multiple cellular proteins involved in transmembrane nutrient uptake (cholesterol, fatty acid, glucose, etc.), cell-signaling, immune recognition, pathogen entry, and many other roles. Despite these advances, however, relatively little is known regarding the organization of cholesterol itself in these plasma membrane microdomains. Although a variety of non-sterol markers indicate the presence of microdomains in the plasma membranes of living cells, none of these studies have demonstrated that cholesterol is enriched in these microdomains in living cells. Further, the role of cholesterol-rich membrane microdomains as targets for intracellular cholesterol trafficking proteins such as sterol carrier protein-2 (SCP-2) that facilitate cholesterol uptake and transcellular transport for targeting storage (cholesterol esters) or efflux is only beginning to be understood. Herein, we summarize the background as well as recent progress in this field that has advanced our understanding of these issues.