School of Graduate Studies, Molecular and Cell Biology Program, State University of New York Downstate Medical Center, Brooklyn, NY.
New York University Winthrop Hospital, Mineola, NY and Veterans Affairs New York Harbor Healthcare System, Brooklyn, NY
J Lipid Res. 2018 Jul;59(7):1094-1102. doi: 10.1194/jlr.R083451. Epub 2018 Apr 12.
A better understanding of intracellular lipoprotein assembly may help identify proteins with important roles in lipid disorders. apoB-containing lipoproteins (B-lps) are macromolecular lipid and protein micelles that act as specialized transport vehicles for hydrophobic lipids. They are assembled predominantly in enterocytes and hepatocytes to transport dietary and endogenous fat, respectively, to different tissues. Assembly occurs in the endoplasmic reticulum (ER) and is dependent on lipid resynthesis in the ER and on a chaperone, namely, microsomal triglyceride transfer protein (MTTP). Precursors for lipid synthesis are obtained from extracellular sources and from cytoplasmic lipid droplets. MTTP is the major and essential lipid transfer protein that transfers phospholipids and triacylglycerols to nascent apoB for the assembly of lipoproteins. Assembly is aided by cell death-inducing DFF45-like effector B and by phospholipid transfer protein, which may facilitate additional deposition of triacylglycerols and phospholipids, respectively, to apoB. Here, we summarize the current understanding of the different steps in the assembly of B-lps and discuss the role of lipid transfer proteins in these steps to help identify new clinical targets for lipid-associated disorders, such as heart disease.
更好地了解细胞内脂蛋白的组装可能有助于确定在脂质紊乱中具有重要作用的蛋白质。载脂蛋白 B 包含的脂蛋白 (B-lps) 是作为疏水性脂质的特殊运输载体的大分子脂质和蛋白质胶束。它们主要在肠细胞和肝细胞中组装,分别将膳食和内源性脂肪运输到不同的组织。组装发生在内质网 (ER) 中,依赖于 ER 中的脂质重新合成和伴侣,即微粒体甘油三酯转移蛋白 (MTTP)。脂质合成的前体来自细胞外来源和细胞质脂滴。MTTP 是主要和必需的脂质转移蛋白,它将磷脂和三酰基甘油转移到新生的 apoB 上,用于脂蛋白的组装。细胞死亡诱导 DFF45 样效应因子 B 和磷脂转移蛋白有助于 apoB 上分别沉积更多的三酰基甘油和磷脂,从而辅助组装。在这里,我们总结了 B-lps 组装的不同步骤的当前理解,并讨论了脂质转移蛋白在这些步骤中的作用,以帮助确定与脂质相关的疾病(如心脏病)的新临床靶点。