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跨膜糖蛋白 CD36(SR-B2)在细胞脂肪酸摄取和利用中的动态作用。

Dynamic role of the transmembrane glycoprotein CD36 (SR-B2) in cellular fatty acid uptake and utilization.

机构信息

Department of Genetics and Cell Biology, Faculty of Health, Medicine & Life Sciences (FHML), Maastricht University, 6200 MD Maastricht, The Netherlands

Department of Genetics and Cell Biology, Faculty of Health, Medicine & Life Sciences (FHML), Maastricht University, 6200 MD Maastricht, The Netherlands.

出版信息

J Lipid Res. 2018 Jul;59(7):1084-1093. doi: 10.1194/jlr.R082933. Epub 2018 Apr 7.

Abstract

The widely expressed transmembrane glycoprotein, cluster of differentiation 36 (CD36), a scavenger receptor class B protein (SR-B2), serves many functions in lipid metabolism and signaling. Here, we review CD36's role in facilitating cellular long-chain fatty acid uptake across the plasma membrane, particularly in heart and skeletal muscles. CD36 acts in concert with other membrane proteins, such as peripheral plasma membrane fatty acid-binding protein, and is an intracellular docking site for cytoplasmic fatty acid-binding protein. The cellular fatty-acid uptake rate is governed primarily by the presence of CD36 at the cell surface, which is regulated by the subcellular vesicular recycling of CD36 from endosomes to the plasma membrane. CD36 has been implicated in dysregulated fatty acid and lipid metabolism in pathophysiological conditions, particularly in high-fat diet-induced insulin resistance and diabetic cardiomyopathy. Current research is exploring signaling pathways and vesicular trafficking routes involving CD36 to identify metabolic targets to manipulate the cellular utilization of fatty acids. Because of its rate-controlling function in the use of fatty acids in the heart and muscle, CD36 would be a preferable target to protect myocytes against lipotoxicity. Despite a poor understanding of its mechanism of action, CD36 has emerged as a pivotal membrane protein involved in whole-body lipid homeostasis.

摘要

广泛表达的跨膜糖蛋白,分化簇 36(CD36),一种清道夫受体 B 类蛋白(SR-B2),在脂质代谢和信号转导中具有多种功能。在这里,我们回顾了 CD36 在促进细胞长链脂肪酸穿过质膜摄取方面的作用,特别是在心脏和骨骼肌中。CD36 与其他膜蛋白(如外周质膜脂肪酸结合蛋白)协同作用,是细胞质脂肪酸结合蛋白的细胞内对接位点。细胞脂肪酸摄取率主要由细胞表面 CD36 的存在决定,CD36 从内体到质膜的亚细胞小泡再循环受到调节。CD36 与病理生理条件下脂肪酸和脂质代谢失调有关,特别是在高脂肪饮食诱导的胰岛素抵抗和糖尿病心肌病中。目前的研究正在探索涉及 CD36 的信号通路和小泡运输途径,以确定代谢靶点来操纵细胞对脂肪酸的利用。由于其在心脏和肌肉中脂肪酸利用中的限速作用,CD36 将是保护心肌细胞免受脂毒性的首选靶标。尽管对其作用机制的了解很差,但 CD36 已成为涉及全身脂质稳态的关键膜蛋白。

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