Synthesis, Fate, and Proposed Function of Clusterin (SGP-2) in the Testis

Clusterin (SGP-2) is the major protein in the spent medium of rat Sertoli cell cultures (1,2). Rat clusterin is a glycoprotein of pI approximately 4.0 and is made up of two nonidentical disulfide-linked subunits of 34 kD and 47 kD with extensive charge heterogeneity (3,4). The highly negative charge and overall charge heterogeneity of the protein have been attributed to sulfation of the carbohydrate moieties and the presence of sialic acid (5). The cDNA sequence obtained after immunoprecipitation of polysomes and cloning of the mRNA contained an open reading frame sufficient in length to code for both monomers (4). It was shown that clusterin is made as a full-length precursor, undergoes posttranslational modifications, and is cleaved into two disulfide-linked subunits prior to secretion. Northern analysis of RNA from Sertoli cells with probes generated from the cDNA revealed a 2 kb message present in high abundance in testis, epididymis, and in Sertoli cells in culture (4). A similar-sized transcript was also observed in many other tissues. A search of nucleic acid and protein databases at the time revealed no identities with known sequences (see Fig. 7.1 for more structural information).