STRUCTURE AND FUNCTION OF GP-330

GP-330的结构和功能

• 批准号: 2016646
• 负责人: ROBERT T MCCLUSKEY
• 金额: $ 23.72万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-12-15 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2016646
• 关键词: antigen receptors; autoantibody; complementary DNA; epithelium; glycoprotein structure; glycoproteins; immune complex diseases; laboratory rat; low density lipoprotein receptor; membranous glomerulonephritis; monoclonal antibody; nucleic acid sequence; polymerase chain reaction; protein structure function; receptor mediated endocytosis; southern blotting; transfection

The main goal of this project is to investigate the structure, function and pathogenic role of a large glycoprotein called gp 330. This molecule was first identified as a major pathogenic antigen in Heymann nephritis - a rat model of human membranous glomerulonephritis. In a later study, the primary structure of gp 330, as deduced from partial cDNAs, was found to have considerable homology to the low density lipoprotein (LDL) receptor and the LDL receptor related protein (LRP), also known as the alpha2 macroglobulin receptor (alpha2MR). Recently, it has been shown that several known ligands of LRP/alpha2 MR bind to gp 330 in vitro, but the physiologic relevance of these observations is unknown, since gp 330 and LRP/alpha2MR have quite different distributions in vivo. Gp 330 is largely restricted to a group of epithelial cells whose major function appears to be absorption. A 39-44 KD protein invariably co-purifies with gp 330 and LRP/alpha2MR; this receptor associated protein (alpha2MRAP) inhibits the binding of ligands to gp 330 or LRP/alpha2MR in vitro, but its role in vivo is unknown. Major goals of this project are to obtain a full length cDNA encoding gp 330, investigate its receptor function in vivo, and to clarify the function of alpha2MRAP. In addition, the role of alpha2MRAP, gp 330 and ligands of gp 330 in the development of immune deposits in Heymann nephritis will be studied. The research may provide information about the receptor function of gp 330 and its role in specialized epithelial cells. The studies on Heymann nephritis should reveal new information about how immune deposits form in glomeruli, which is an important mechanism in major forms of human glomerulonephritis.

该项目的主要目标是研究结构，功能 和称为GP 330的大糖蛋白的致病作用。该分子 首先被确定为海曼肾炎中的主要致病抗原 - 人膜​​肾小球肾炎的大鼠模型。在以后的研究中 从部分cDNA推论的GP 330的主要结构已被发现为 与低密度脂蛋白（LDL）受体具有相当大的同源性 和LDL受体相关蛋白（LRP），也称为alpha2 大球蛋白受体（α2MR）。最近，已经表明 LRP/alpha2 MR的几种已知配体在体外与GP 330结合，但 这些观察结果的生理相关性是未知的，因为GP 330和 LRP/alpha2MR在体内具有截然不同的分布。 GP 330主要是 仅限于一组主要功能的上皮细胞 吸收。 39-44 kD蛋白总是与GP 330并发 LRP/Alpha2Mr;该受体相关蛋白（α2MRAP）抑制 在体外，配体与GP 330或LRP/alpha2MR的结合，但其作用在 体内未知。 该项目的主要目标是获得编码GP的全长cDNA 330，研究其体内受体功能，并阐明 alpha2mrap的功能。此外，Alpha2Mrap，GP 330和 GP 330的配体在Heymann的免疫沉积物发展中 将研究肾炎。研究可能会提供有关 GP 330的受体功能及其在专门上皮细胞中的作用。 关于海曼肾炎的研究应揭示有关如何 肾小球形成免疫沉积物，这是一个重要的机制 人肾小球肾炎的主要形式。

项目成果

Binding of the low density lipoprotein receptor-associated protein (RAP) to thyroglobulin (Tg): putative role of RAP in the Tg secretory pathway.

低密度脂蛋白受体相关蛋白 (RAP) 与甲状腺球蛋白 (Tg) 的结合：RAP 在 Tg 分泌途径中的假定作用。

• DOI: 10.1210/mend.15.10.0710
• 发表时间: 2001
• 期刊: Molecular endocrinology (Baltimore, Md.)
• 作者: Marino,M;Chiovato,L;Lisi,S;Pinchera,A;McCluskey,RT
• 通讯作者: McCluskey,RT

Megalin (gp330) is an endocytic receptor for thyroglobulin on cultured fisher rat thyroid cells.

Megalin (gp330) 是培养的渔鼠甲状腺细胞上甲状腺球蛋白的内吞受体。

• DOI: 10.1074/jbc.274.18.12898
• 发表时间: 1999
• 期刊: The Journal of biological chemistry
• 作者: Marinò,M;Zheng,G;McCluskey,RT
• 通讯作者: McCluskey,RT

Expression of gp330 and gp330/alpha 2-macroglobulin receptor-associated protein in renal tubular differentiation.

gp330 和 gp330/α2-巨球蛋白受体相关蛋白在肾小管分化中的表达。

• DOI: 10.1681/asn.v4122003
• 发表时间: 1994
• 期刊: Journal of the American Society of Nephrology : JASN
• 作者: Abbate,M;Bachinsky,DR;McCluskey,RT;Brown,D
• 通讯作者: Brown,D

Comparison of anti-GBM antibodies in sera with or without ANCA.

有或没有 ANCA 的血清中抗 GBM 抗体的比较。

• DOI: 10.1681/asn.v83376
• 发表时间: 1997
• 期刊: Journal of the American Society of Nephrology : JASN
• 作者: Hellmark,T;Niles,JL;Collins,AB;McCluskey,RT;Brunmark,C
• 通讯作者: Brunmark,C

gp330: receptor and autoantigen.

gp330：受体和自身抗原。

• DOI: 10.1111/j.1749-6632.1994.tb44309.x
• 发表时间: 1994
• 期刊: Annals of the New York Academy of Sciences
• 影响因子: 5.2
• 作者: Zheng,G;Bachinsky,DR;Abbate,M;Andres,G;Brown,D;Stamenkovic,I;Niles,JL;McCluskey,RT
• 通讯作者: McCluskey,RT