Fong Loren G, Young Stephen G, Beigneux Anne P, Bensadoun André, Oberer Monika, Jiang Haibo, Ploug Michael
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Trends Endocrinol Metab. 2016 Jul;27(7):455-469. doi: 10.1016/j.tem.2016.04.013. Epub 2016 May 14.
GPIHBP1, a GPI-anchored protein in capillary endothelial cells, is crucial for the lipolytic processing of triglyceride-rich lipoproteins (TRLs). GPIHBP1 shuttles lipoprotein lipase (LPL) to its site of action in the capillary lumen and is essential for the margination of TRLs along capillaries - such that lipolytic processing can proceed. GPIHBP1 also reduces the unfolding of the LPL catalytic domain, thereby stabilizing LPL catalytic activity. Many different GPIHBP1 mutations have been identified in patients with severe hypertriglyceridemia (chylomicronemia), the majority of which interfere with folding of the protein and abolish its capacity to bind and transport LPL. The discovery of GPIHBP1 has substantially revised our understanding of intravascular triglyceride metabolism but has also raised many new questions for future research.
GPIHBP1是一种存在于毛细血管内皮细胞中的糖基磷脂酰肌醇（GPI）锚定蛋白，对富含甘油三酯的脂蛋白（TRL）的脂解过程至关重要。GPIHBP1将脂蛋白脂肪酶（LPL）转运至其在毛细血管腔中的作用位点，对于TRL沿毛细血管的边缘化至关重要，从而使脂解过程能够进行。GPIHBP1还减少LPL催化结构域的解折叠，从而稳定LPL的催化活性。在严重高甘油三酯血症（乳糜微粒血症）患者中已鉴定出许多不同的GPIHBP1突变，其中大多数会干扰蛋白质的折叠并消除其结合和转运LPL的能力。GPIHBP1的发现极大地改变了我们对血管内甘油三酯代谢的理解，但也提出了许多新的未来研究问题。
