SGP-2 (CLUSTERIN) AND REPRODUCTION

培养的支持细胞分泌的主要蛋白质之一是

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.