SGP-2 (CLUSTERIN) AND REPRODUCTION

SGP-2（簇蛋白）和繁殖

• 批准号: 2203017
• 负责人: MICHAEL D GRISWOLD
• 金额: $ 13.5万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-07-01 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2203017
• 关键词: SGP; CLUSTERIN; REPRODUCTION

One of the major secreted proteins from cultured Sertoli cells has been designated as sulfated glycoprotein-2 or SGP-2. This protein is synthesized as a singly polypeptide which is extensively glycosylated and is cleaved on secretion into two disulfide linked subunits. The function of SGP-2 is unknown although it has been implicated in apotosis, apolipoprotein structure, chromaffin granule structure and complement inhibition. It is induced in a number of disease processes including renal diseases, Alzheimer's disease, several forms of neurodegeneration and in neural tumors. The structure of the protein suggests that it can interact with lipids or hydrophobic regions of macromolecule. Our current working hypothesis is that SGP-2 is involved in the movement of lipids between cells. In the testis we feel that it is involved in membrane remodeling processes involved in the development and maturation of spermatozoa. We believe that SGP-2 forms macromolecular complexes which are different from the apo J complexes described by deSilva et al, 1991. We presume that the inductive response of SGP-2 to cellular damage is a response to components of cell membranes that are released during cellular damage. We predict that the specific uptake and removal of SGP- 2 from testicular fluids is important in the overall function and is mediated by the N-linked oligosaccharide that is part of its structure. Experiments in this proposal will first examine the oligosaccharide and the nature of the sulfation of SGP-2 as well as the alignment of the disulfide bonds. The second specific aim is directed towards the elucidation of the functional form of SGP-2 in the macromolecular complexes of the testis. The final specific aim will examine the regulation of the SGP-2 gene by examining the response of promoter- reporter gene constructs in a Sertoli cell line. The goal of this part of the proposed studies will be determine the region of the gene and the nature of the signalling molecules responsible for the response to cell damage.

来自培养的Sertoli细胞的主要分泌蛋白之一是 被指定为硫酸化糖蛋白-2或SGP-2。 该蛋白是 合成为单一多肽，已广泛糖基化，并且 分泌分为两个二硫键连接的亚基。 功能 SGP-2的尚不清楚，尽管它与凋亡有关，但 载脂蛋白结构，染色体颗粒结构和补体 抑制。 它是在许多疾病过程中引起的 肾脏疾病，阿尔茨海默氏病，几种形式的神经变性 和神经肿瘤。 蛋白质的结构表明它可以 与大分子的脂质或疏水区相互作用。 我们的 当前的工作假设是SGP-2参与了 细胞之间的脂质。 在睾丸中，我们认为它参与了 涉及开发和成熟的膜重塑过程 精子。 我们认为SGP-2形成大分子复合物 与Desilva等人描述的Apo J复合物不同， 1991。我们认为SGP-2对细胞损伤的电感反应 是对在释放的细胞膜组件的响应 细胞损伤。 我们预测，SGP-的特定摄取和去除 2来自睾丸液在整体功能中很重要，为 由N-连接的寡糖介导，该寡糖是其结构的一部分。 该提案中的实验将首先检查寡糖和 SGP-2硫酸的性质以及 二硫键。 第二个特定目标是针对 大分子中SGP-2的功能形式阐明 睾丸的复合物。 最终的具体目的将检查 通过检查启动子的反应来调节SGP-2基因 记者基因构建在Sertoli细胞系中。 这部分的目标 在拟议的研究中，将确定基因的区域和 负责对细胞反应的信号分子的性质 损害。