Sellers Jeremy A, Hou Li, Schoenberg Daniel R, Batistuzzo de Medeiros Silvia R, Wahli Walter, Shelness Gregory S
Department of Pathology, Wake Forest University School of Medicine Winston-Salem, North Carolina 27157-1040, USA.
J Biol Chem. 2005 Apr 8;280(14):13902-5. doi: 10.1074/jbc.M500769200. Epub 2005 Jan 27.
Vitellogenins (Vtg) are ancient lipid transport and storage proteins and members of the large lipid transfer protein (LLTP) gene family, which includes insect apolipophorin II/I, apolipoprotein B (apoB), and the microsomal triglyceride transfer protein (MTP). Lipidation of Vtg occurs at its site of synthesis in vertebrate liver, insect fat body, and nematode intestine; however, the mechanism of Vtg lipid acquisition is unknown. To explore whether Vtg biogenesis requires the apoB cofactor and LLTP family member, MTP, Vtg was expressed in COS cells with and without coexpression of the 97-kDa subunit of human MTP. Expression of Vtg alone gave rise to a approximately 220-kDa apoprotein, which was predominantly confined to an intracellular location. Coexpression of Vtg with human MTP enhanced Vtg secretion by 5-fold, without dramatically affecting its intracellular stability. A comparison of wild type and a triglyceride transfer-defective form of MTP revealed that both were capable of promoting Vtg secretion, whereas only wild type MTP could promote the secretion of apoB41 (amino-terminal 41% of apoB). These studies demonstrate that the biogenesis of Vtg is MTP-dependent and that MTP is the likely ancestral member of the LLTP gene family.
卵黄原蛋白（Vtg）是古老的脂质转运和储存蛋白，属于大型脂质转运蛋白（LLTP）基因家族成员，该家族包括昆虫载脂蛋白II/I、载脂蛋白B（apoB）和微粒体甘油三酯转运蛋白（MTP）。Vtg的脂化发生在脊椎动物肝脏、昆虫脂肪体和线虫肠道的合成部位；然而，Vtg获取脂质的机制尚不清楚。为了探究Vtg的生物合成是否需要apoB辅助因子和LLTP家族成员MTP，在有和没有共表达人MTP 97 kDa亚基的情况下，在COS细胞中表达Vtg。单独表达Vtg产生了一种约220 kDa的载脂蛋白，其主要局限于细胞内位置。Vtg与人MTP共表达可使Vtg分泌增加5倍，而不会显著影响其细胞内稳定性。野生型MTP和甘油三酯转运缺陷型MTP的比较表明，两者都能够促进Vtg分泌，而只有野生型MTP能够促进apoB41（apoB的氨基末端41%）的分泌。这些研究表明，Vtg的生物合成依赖于MTP，并且MTP可能是LLTP基因家族的祖先成员。
