The Story of SPATA2 (Spermatogenesis-Associated Protein 2): From Sertoli Cells to Pancreatic Beta-Cells

In an attempt to isolate new spermatogenesis-associated genes, pd1 was initially identified and cloned as a novel human cDNA sequence from testis cDNA library. The novel gene was submitted to GenBank under accession n° U28164 in 1996. PD1 expression was demonstrated at the Sertoli cell level with a production which appeared to be under the influence of neighbouring spermatogenic cells. The rat orthologue of human pd1 was further cloned and, according to the Gene Nomenclature Committee, was renamed spata2 (spermatogenesis-associated protein 2) gene on the basis of its FSH-dependent up-regulation and developmental expression. The analysis of the human and rat cDNA sequences disclosed an open reading frame for a protein of 520 and 511 amino acids respectively, with an overall identity of 85%. Subsequently, a zebrafish orthologue of the human spata2 gene was identified. The consensus open reading frame (1650 bp) encodes a polypeptide of 550 amino acids, which shares 37% identity with the human spata2. By means of whole-mount in situ hybridisation it has been shown that spata2 transcripts are maternally derived and become strongly localised in the central nervous system at early developmental stages. At the same time, RT-PCR analysis demonstrated that several adult zebrafish tissues expressed high level of spata2 mRNA providing evidence that this gene may have a broader function than previously described. More recently, novel findings have highlighted a potential role of spata2 during pancreatic development and β-cell proliferation. In this review we will discuss spata2 gene expression and regulation as well as focus on novel evidence, which suggests a role for this protein in pancreatic β-cell function.