Endoplasmic reticulum quality control in lipoprotein metabolism
Endoplasmic reticulum quality control in lipoprotein metabolism
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DOI：
10.1016/j.mce.2019.110547
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发表时间：
2019-12-01
影响因子：
4.1
通讯作者：
Neher, Saskia B.
中科院分区：
文献类型：
--
作者：
Koerner, Cari M.;Roberts, Benjamin S.;Neher, Saskia B.
脂质在能量代谢中发挥着关键作用，需要一套蛋白质将脂质输送到组织。其中一些蛋白质需要复杂的内质网 (ER) 质量控制 (QC) 系统和独特的二级伴侣进行折叠。关键例子包括载脂蛋白 B (apoB)（它是许多脂蛋白的主要支架）、二聚脂肪酶（水解循环脂蛋白中的甘油三酯）以及低密度脂蛋白受体 (LDLR)（清除循环中富含胆固醇的脂蛋白）。 ApoB 需要专门的蛋白质进行脂化，二聚脂肪酶脂蛋白脂肪酶 (LPL) 和肝脂肪酶 (HL) 需要跨膜成熟因子进行分泌，而 LDLR 需要几个专门的、域特异性的伴侣。这些蛋白质或其伴侣的有害突变可能导致血脂异常，这对人类健康有害。在这里，我们回顾了确保 apoB、LPL、HL 和 LDLR 分泌的 ER 质量控制系统，重点关注每种蛋白质所需的专门伴侣。
Lipids play a critical role in energy metabolism, and a suite of proteins is required to deliver lipids to tissues. Several of these proteins require an intricate endoplasmic reticulum (ER) quality control (QC) system and unique secondary chaperones for folding. Key examples include apolipoprotein B (apoB), which is the primary scaffold for many lipoproteins, dimeric lipases, which hydrolyze triglycerides from circulating lipoproteins, and the low-density lipoprotein receptor (LDLR), which clears cholesterol-rich lipoproteins from the circulation. ApoB requires specialized proteins for lipidation, dimeric lipases lipoprotein lipase (LPL) and hepatic lipase (HL) require a transmembrane maturation factor for secretion, and the LDLR requires several specialized, domain-specific chaperones. Deleterious mutations in these proteins or their chaperones may result in dyslipidemias, which are detrimental to human health. Here, we review the ER quality control systems that ensure secretion of apoB, LPL, HL, and LDLR with a focus on the specialized chaperones required by each protein.