Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technology Enterprise (BRITE), College of Arts and Sciences, North Carolina Central University, Durham, NC 27707, USA.
Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Biochem Biophys Res Commun. 2014 Mar 7;445(2):422-7. doi: 10.1016/j.bbrc.2014.02.019. Epub 2014 Feb 12.
Several findings suggest that the low-density lipoprotein (LDL) receptor may internalize different lipoprotein particles via diverse pathways. Using a combination of discontinuous sucrose gradients and Triton solubilization studies, we demonstrated that the LDL receptor could be located simultaneously in clathrin-coated pits and caveolae in rat and human liver and in human hepatocyte-like C3A cells. Treatment with the cholesterol biosynthesis inhibitor, zaragozic acid A, shifted the distribution of the LDL receptor to clathrin containing fractions, whereas treatment with cholesterol or LDL shifted the receptor distribution towards caveolin-1 containing fractions. The LDL-dependent shift of the LDL receptor to caveolae coincided with a reduction in internalization of Bodipy-LDL. Redistribution within plasma membrane microdomains in response to specific treatments resulting in changes in LDL receptor function represents a novel paradigm that could be exploited in the development of a new class of therapeutic drugs.
有几项研究结果表明，低密度脂蛋白（LDL）受体可能通过不同的途径内化不同的脂蛋白颗粒。我们使用不连续蔗糖梯度和 Triton 溶解研究的组合，证明 LDL 受体可以同时存在于大鼠和人肝以及人肝样 C3A 细胞的网格蛋白包被小窝和 caveolae 中。用胆固醇生物合成抑制剂扎拉戈酸 A 处理会将 LDL 受体的分布转移到含网格蛋白的部分，而用胆固醇或 LDL 处理会将受体分布转移到含有 caveolin-1 的部分。LDL 依赖性 LDL 受体向 caveolae 的转移与 Bodipy-LDL 的内化减少同时发生。由于特定处理导致 LDL 受体功能发生变化而在质膜微域内重新分布，代表了一种新的范例，可用于开发一类新的治疗药物。
