Department of Cell Biology and Pediatrics, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA.
Nutr Metab (Lond). 2012 Feb 21;9:14. doi: 10.1186/1743-7075-9-14.
Microsomal triglyceride transfer protein (MTP) was first identified as a major cellular protein capable of transferring neutral lipids between membrane vesicles. Its role as an essential chaperone for the biosynthesis of apolipoprotein B (apoB)-containing triglyceride-rich lipoproteins was established after the realization that abetalipoproteinemia patients carry mutations in the MTTP gene resulting in the loss of its lipid transfer activity. Now it is known that it also plays a role in the biosynthesis of CD1, glycolipid presenting molecules, as well as in the regulation of cholesterol ester biosynthesis. In this review, we will provide a historical perspective about the identification, purification and characterization of MTP, describe methods used to measure its lipid transfer activity, and discuss tissue expression and function. Finally, we will review the role MTP plays in the assembly of apoB-lipoprotein, the regulation of cholesterol ester synthesis, biosynthesis of CD1 proteins and propagation of hepatitis C virus. We will also provide a brief overview about the clinical potentials of MTP inhibition.
微粒体甘油三酯转移蛋白(MTP)最初被鉴定为一种主要的细胞蛋白,能够在膜泡之间转移中性脂质。在意识到载脂蛋白 B (apoB) 含甘油三酯丰富的脂蛋白的生物合成需要 MTP 作为必需伴侣后,人们发现 abetalipoproteinemia 患者携带 MTP 基因突变,导致其脂质转移活性丧失。现在已知,它还在 CD1、糖脂呈递分子的生物合成以及胆固醇酯生物合成的调节中发挥作用。在这篇综述中,我们将提供 MTP 的鉴定、纯化和表征的历史视角,描述用于测量其脂质转移活性的方法,并讨论组织表达和功能。最后,我们将回顾 MTP 在 apoB-脂蛋白组装、胆固醇酯合成调节、CD1 蛋白生物合成和丙型肝炎病毒传播中的作用。我们还将简要概述 MTP 抑制的临床潜力。