Gin Peter, Beigneux Anne P, Davies Brandon, Young Madeline F, Ryan Robert O, Bensadoun André, Fong Loren G, Young Stephen G
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Biochim Biophys Acta. 2007 Dec;1771(12):1464-8. doi: 10.1016/j.bbalip.2007.10.005. Epub 2007 Oct 22.
GPIHBP1 is an endothelial cell protein that serves as a platform for lipoprotein lipase-mediated processing of triglyceride-rich lipoproteins within the capillaries of heart, adipose tissue, and skeletal muscle. The absence of GPIHBP1 causes severe chylomicronemia. A hallmark of GPIHBP1 is the ability to bind lipoprotein lipase, chylomicrons, and apolipoprotein (apo-) AV. A homozygous G56R mutation in GPIHBP1 was recently identified in two siblings with chylomicronemia, and the authors of that study suggested that the G56R substitution was responsible for the hyperlipidemia. In this study, we created a human GPIHBP1 expression vector, introduced the G56R mutation, and tested the ability of the mutant GPIHBP1 to reach the cell surface and bind lipoprotein lipase, chylomicrons, and apo-AV. Our studies revealed that the G56R substitution did not affect the ability of GPIHBP1 to reach the cell surface, nor did the amino acid substitution have any discernible effect on the binding of lipoprotein lipase, chylomicrons, or apo-AV.
GPIHBP1是一种内皮细胞蛋白，它作为脂蛋白脂肪酶介导的富含甘油三酯脂蛋白在心脏、脂肪组织和骨骼肌毛细血管内加工处理的平台。GPIHBP1的缺失会导致严重的乳糜微粒血症。GPIHBP1的一个特点是能够结合脂蛋白脂肪酶、乳糜微粒和载脂蛋白（apo-）AV。最近在两名患有乳糜微粒血症的兄弟姐妹中发现了GPIHBP1中的纯合G56R突变，该研究的作者认为G56R替代是导致高脂血症的原因。在本研究中，我们构建了一个人GPIHBP1表达载体，引入了G56R突变，并测试了突变型GPIHBP1到达细胞表面以及结合脂蛋白脂肪酶、乳糜微粒和apo-AV的能力。我们的研究表明，G56R替代并不影响GPIHBP1到达细胞表面的能力，并且该氨基酸替代对脂蛋白脂肪酶、乳糜微粒或apo-AV的结合也没有任何明显影响。
