Role of the adaptor protein PDZK1 in controlling the HDL receptor SR-BI.
Role of the adaptor protein PDZK1 in controlling the HDL receptor SR-BI.
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DOI：
10.1097/mol.0b013e32832aee82
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发表时间：
2009-06
影响因子：
4.4
通讯作者：
Krieger M
中科院分区：
文献类型：
--
作者：
Kocher O;Krieger M
脂蛋白受体活性的调节影响脂蛋白代谢、相关生理学和病理生理学。与低密度脂蛋白或高密度脂蛋白受体结合的接头蛋白显然将这些受体与其正常运作所必需的细胞成分联系在一起。在这里，我们重点介绍了PDZK1对高密度脂蛋白受体SR-BI的影响，重点介绍了其各个PDZ结构域的作用、对高密度脂蛋白代谢的影响以及与心血管疾病的相关性。PDZK1在维持肝脏SR-BI水平和控制高密度脂蛋白代谢，防止动脉粥样硬化的发展，以及通过高密度脂蛋白介导SR-BI依赖的内皮细胞生物学调节方面发挥重要作用，提示PDZK1在正常生理中发挥多种作用，并可能影响相关的病理。PDZK1的四个PDZ结构域似乎都是促进正常肝脏表达、功能和SR-BI细胞内定位所必需的。SR-BI调节高密度脂蛋白代谢和功能的一些特征，其中一些依赖于SR-BI与PDZK1的相互作用。探索PDZK1的结构和功能及其控制SR-BI的机制将提供对高密度脂蛋白代谢的更多见解，并可能为心血管疾病的新治疗方式提供基础。
Regulation of lipoprotein receptor activity influences lipoprotein metabolism, related physiology and pathophysiology. Adaptor proteins that bind to the LDL or HDL receptors apparently link these receptors to cellular components essential for their normal functioning. Here we focus on the influence of PDZK1 on the HDL receptor SR-BI, with emphasis on the roles played by its individual PDZ domains, the impact in regulating HDL metabolism and the relevance for cardiovascular disease. PDZK1 plays an essential role in maintaining hepatic SR-BI levels and controlling HDL metabolism, protects against the development of atherosclerosis in a murine model and also mediates SR-BI-dependent regulation of endothelial cell biology by HDL, suggesting that PDZK1 plays multiple roles in normal physiology and may influence associated pathology. All four PDZ domains of PDZK1 appear necessary to promote normal hepatic expression, function and intracellular localization of SR-BI. SR-BI mediates several features of HDL metabolism and function, some of which depend on SR-BI’s interaction with PDZK1. Exploration of the structure and function of PDZK1 and the mechanisms by which it controls SR-BI will provide additional insights into HDL metabolism and may provide the basis for new therapeutic modalities for cardiovascular disease.