SGP-2 (CLUSTERIN) AND REPRODUCTION

培养的Sertoli细胞分泌的主要蛋白质之一是 被指定为硫酸糖蛋白-2或SGP-2。这种蛋白质是 合成为一种广泛糖基化的单一多肽 在分泌时被裂解成两个二硫键连接的亚基。该功能 SGP-2的表达虽然与细胞凋亡有关，但仍不清楚， 载脂蛋白结构、嗜铬颗粒结构与补体 抑制力。它在许多疾病过程中被诱导，包括 肾脏疾病，阿尔茨海默病，几种形式的神经退行性变 在神经肿瘤中。蛋白质的结构表明它可以 与脂类或大分子疏水区域相互作用。我们的 目前的工作假说是SGP-2参与了 细胞间的脂类。在睾丸中，我们感觉它参与了 参与发育和成熟的膜重塑过程 精子的数量。我们认为SGP-2形成了大分子复合体 其不同于DeSilva等人描述的载脂蛋白J络合物， 1991年。我们推测SGP-2对细胞损伤的诱导反应 是对细胞膜成分的反应，这些成分在 细胞损伤。我们预测SGP-的特异性摄取和清除 从睾丸液中提取的2在整体功能上很重要 由作为其结构一部分的N-连接低聚糖介导。 该方案中的实验将首先检查低聚糖和 SGP-2的硫酸盐化性质以及SGP-2 二硫键。第二个具体目标是针对 SGP-2在大分子中功能形式的阐明 睾丸的复合体。最终的具体目标将审查 通过检测启动子-2的反应来调控SGP-2基因 报告基因在Sertoli细胞系中构建。这一部分的目标是 拟议的研究中将确定该基因的区域和 负责细胞反应的信号分子的性质 损坏。

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.