Department of Medicine, University of California, Los Angeles, CA 90095, USA.
J Lipid Res. 2011 Nov;52(11):1869-84. doi: 10.1194/jlr.R018689. Epub 2011 Aug 15.
Interest in lipolysis and the metabolism of triglyceride-rich lipoproteins was recently reignited by the discovery of severe hypertriglyceridemia (chylomicronemia) in glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1)-deficient mice. GPIHBP1 is expressed exclusively in capillary endothelial cells and binds lipoprotein lipase (LPL) avidly. These findings prompted speculation that GPIHBP1 serves as a binding site for LPL in the capillary lumen, creating "a platform for lipolysis." More recent studies have identified a second and more intriguing role for GPIHBP1-picking up LPL in the subendothelial spaces and transporting it across endothelial cells to the capillary lumen. Here, we review the studies that revealed that GPIHBP1 is the LPL transporter and discuss which amino acid sequences are required for GPIHBP1-LPL interactions. We also discuss the human genetics of LPL transport, focusing on cases of chylomicronemia caused by GPIHBP1 mutations that abolish GPIHBP1's ability to bind LPL, and LPL mutations that prevent LPL binding to GPIHBP1.
人们对脂肪分解和富含甘油三酯的脂蛋白代谢的兴趣最近因糖基磷脂酰肌醇锚定高密度脂蛋白结合蛋白 1（GPIHBP1）缺陷小鼠中严重的高甘油三酯血症（乳糜微粒血症）的发现而重新燃起。GPIHBP1 仅在毛细血管内皮细胞中表达，并与脂蛋白脂肪酶（LPL）强烈结合。这些发现促使人们推测 GPIHBP1 作为 LPL 在毛细血管腔中的结合位点，形成“脂肪分解的平台”。最近的研究发现了 GPIHBP1 的第二个更有趣的作用——在血管内皮细胞下腔中拾取 LPL 并将其转运穿过内皮细胞到毛细血管腔。在这里，我们回顾了揭示 GPIHBP1 是 LPL 转运蛋白的研究，并讨论了 GPIHBP1-LPL 相互作用所需的氨基酸序列。我们还讨论了 LPL 转运的人类遗传学，重点关注 GPIHBP1 突变导致 GPIHBP1 丧失与 LPL 结合能力的乳糜微粒血症病例，以及阻止 LPL 与 GPIHBP1 结合的 LPL 突变。
