Identification and functional analysis of the LDL receptor gene family members

LDL受体基因家族成员的鉴定及功能分析

基本信息

批准号：
07557177
负责人：
SAITO Yasushi
金额：
$ 4.67万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557177/
关键词：
gene family LDL receptor cloning cDNA apo (protein) E multifunctionality

项目摘要

Receptors belonging to the LDL receptor gene family are playing key roles for wide varied species in cellular endocytosis of a broad spectrum of ligands including spent, biologically inactive and/or unwanted plasmatic carrier complexes, certain toxins, yolk precursors, as well as circulating plasma lipoproteins. We now have discovered and characterized a novel multidomain protein and classified it as a member of the LDL receptor gene family. The -250kDa membrane protein, termed LR11, contains a cluster of 11 LDL receptor ligand binding repeats, a rgoup of 5 LDL receptor "YWTD" repeats, a large hexarepeat domain of structural elements found in neural cell adhesion molecules, and a domain with similarity to a yeast receptor for vacuolar protein sorting, VPS10. The cytoplasmic domain exhibits features typical of endocytosis-competent coated-pit receptors. The mosaic, and presumably multifunctional, receptor is expressed abundantly in brain, liver and adrenal glands. Ligand blotting of LR11-transfected cells demonstrated that LR11 binds apolipoproteinE-containing lipoproteins, as well as other members of LDL receptor gene family. In contrast to the LDL receptor, the mRNA levels in rabbit liver is unaffected by hyperlipidemia. At present, we have no idea which ligand (s) may be the true physiological partner (s) of LR11. However, the localization of rabbit LR11 in the hippocampus, dentate gyrus and cerebral cortex suggests functional significance of LR11 in metabolically active regions of brain. The novel complex mosaic structure of LR11 sheds new lights on the evolution and proposed multifunctionality of the LDLR gene family.

属于LDL受体基因家族的受体在各种物种中发挥了关键作用，在各种配体的细胞内吞作用中，包括花费，生物学上无活性和/或不必要的等离子体载体复合物，某些毒素，蛋黄，蛋黄，蛋黄的前体，以及循环血浆lipopropropopropoprotins。现在，我们发现并表征了一种新型的多域蛋白，并将其归类为LDL受体基因家族的成员。 -250KDA膜蛋白称为LR11，包含11 LDL受体配体结合重复序列的簇，这是一个5 LDL受体“ YWTD”重复序列的Rgoup，这是一个在神经细胞粘附分子和类似于Yeast受体的神经细胞粘附分子中构成的结构元件的大六方蛋白epeat域，用于与YEAST相似。细胞质结构域具有典型的内吞作用涂层受体的特征。镶嵌和大概是多功能的受体在大脑，肝脏和肾上腺中大量表达。 LR11转染细胞的配体印迹表明，LR11结合了含载脂蛋白的脂蛋白以及LDL受体基因家族的其他成员。与LDL受体相反，兔肝脏中的mRNA水平不受高脂血症的影响。目前，我们不知道哪种配体可能是LR11的真正生理伴侣。然而，兔LR11在海马，齿状回和脑皮质中的定位表明LR11在大脑代谢活性区域中的功能意义。 LR11的新型复杂镶嵌结构在Evolution和拟议的LDLR基因家族的多功能性上阐明了新的灯光。