Cluster of differentiation 36 (CD36) is a scavenger receptor (SR), recognizing diverse extracellular ligands in various types of mammalian cells. Long-chain fatty acids (FAs), which are important constituents of phospholipids and triglycerides, also utilize CD36 as a predominant membrane transporter, being incorporated from the circulation across the plasma membrane in several cell types, including cardiac and skeletal myocytes and adipocytes. CD36 is localized in intracellular vesicles as well as the plasma membrane, and its distribution is modulated by extracellular stimuli. Herein, we aimed to clarify the molecular basis of insulin-stimulated translocation of CD36, which leads to the enhanced uptake of long-chain FAs, in adipocytes. To this end, we developed a novel exofacial epitope-tagged reporter to specifically detect cell surface-localized CD36. By employing this reporter, we demonstrate that the small GTPase Rac1 plays a pivotal role in insulin-stimulated translocation of CD36 to the plasma membrane in 3T3-L1 adipocytes. Additionally, phosphoinositide 3-kinase and the protein kinase Akt2 are shown to be involved in the regulation of Rac1. Downstream of Rac1, another small GTPase RalA directs CD36 translocation. Collectively, these results suggest that CD36 is translocated to the plasma membrane by insulin through mechanisms similar to those for the glucose transporter GLUT4 in adipocytes.

中文翻译：

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胰岛素刺激的脂肪酸转运蛋白 CD36 易位至质膜是由脂肪细胞中的小 GTPase Rac1 介导的

分化簇 36 (CD36) 是一种清道夫受体 (SR)，可识别各种类型哺乳动物细胞中的多种细胞外配体。长链脂肪酸 (FA) 是磷脂和甘油三酯的重要成分，也利用 CD36 作为主要的膜转运蛋白，从循环中跨过质膜进入多种细胞类型，包括心肌细胞、骨骼肌细胞和脂肪细胞。CD36 位于细胞内囊泡和质膜中，其分布受到细胞外刺激的调节。在此，我们的目的是阐明胰岛素刺激的 CD36 易位的分子基础，从而导致脂肪细胞中长链 FA 的摄取增强。为此，我们开发了一种新型外表面表位标记报告基因来特异性检测细胞表面定位的 CD36。通过使用该报告基因，我们证明小 GTPase Rac1 在胰岛素刺激的 3T3-L1 脂肪细胞中 CD36 易位至质膜中发挥着关键作用。此外，磷酸肌醇 3-激酶和蛋白激酶 Akt2 也被证明参与 Rac1 的调节。Rac1 的下游，另一个小 GTP 酶 RalA 指导 CD36 易位。总的来说，这些结果表明 CD36 通过类似于脂肪细胞中葡萄糖转运蛋白 GLUT4 的机制被胰岛素转运到质膜。