RGS22, A Novel Testis-Specific Regulator of G-protein Signaling Involved in Human and Mouse Spermiogenesis along with GNA12/13 Subunits1

Abstract

The heterotrimeric G-protein pathway controls numerous cellular processes, including proliferation, differentiation, migration, membrane trafficking, and embryonic development. Regulator of G-protein signaling (RGS) proteins are known to function at the G-protein level. Here, the functional role of a novel RGS protein, regulator of G-protein signaling 22 (RGS22), in the testis was investigated at the mRNA and protein levels. Our results demonstrate that RGS22 is a testis-specific gene. However, significantly decreased expression of RGS22 was found in the testes of patients with azoospermia. RGS22 was translated or posttranslationally modified into multiple proteins of different molecular sizes in prokaryocytes as well as in the testes. Its protein (NP_056483) was localized in spermatogenic cells and Leydig cells and could interact with guanine nucleotide binding protein, alpha 12, 13, and 11 (GNA12, GNA13, and GNA11). Fragmental GFP-fusion protein tracking revealed that the N-terminal of RGS22 was localized in the nucleus. RGS22 and GNA13 were localized in the nucleus from the elongated spermatid stage onward. Indirect immunofluorescence studies revealed defective expression of GNA13 in macrocephalic and global nucleus spermatozoa. These findings suggest that their functions in this subcellular compartment are likely related to the postmeiotic developmental phase, spermiogenesis. RGS22 may also play a role in GNA13 translocation from the cytoplasm to the nucleus during spermiogenesis.