SGP-2 (CLUSTERIN) AND REPRODUCTION

来自培养的支持细胞的主要分泌蛋白之一是 命名为硫酸化糖蛋白-2或SGP-2。 这种蛋白质 作为广泛糖基化的单一多肽合成， 在分泌时被切割成两个二硫键连接的亚基。 功能 尽管SGP-2与细胞凋亡有关， 载脂蛋白结构、嗜铬颗粒结构和补体 抑制作用 它在许多疾病过程中被诱导，包括 肾脏疾病、阿尔茨海默病、几种形式的神经变性 和神经肿瘤。 这种蛋白质的结构表明， 与脂质或大分子疏水区域相互作用。 我们 目前的工作假设是，SGP-2参与了运动， 细胞之间的脂质。 在睾丸中，我们认为它参与了 参与发育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 其不同于deSilva等人描述的载脂蛋白J复合物， 1991. 我们推测SGP-2对细胞损伤的诱导反应 是对细胞膜成分的一种反应， 细胞损伤 我们预测，特定的摄取和清除SGP- 2睾丸液是重要的整体功能， 由作为其结构一部分的N-连接寡糖介导。 本提案中的实验将首先检查低聚糖， SGP-2硫酸化的性质以及 二硫键 第二个具体目标是针对 阐明SGP-2在大分子中的功能形式 睾丸复合体 最后的具体目标将审查 SGP-2基因的调节，通过检查启动子- 在Sertoli细胞系中的报告基因构建体。 本部分的目的 这项研究将确定基因的区域， 负责细胞应答的信号分子的性质 损害

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.