PPM1G dephosphorylates α-catenin to maintain the integrity of adherens junctions and regulates apoptosis in Sertoli cells.

Protein phosphatase, Mg2+/Mn2+ dependent, 1G (PPM1G) regulates protein function via dephosphorylation. PPM1G participates in the assembly of adherens junctions by dephosphorylating α-catenin. Here, we demonstrated through siRNA transfection and intratesticular injection that PPM1G is critical for maintaining blood-testis barrier function and regulating Sertoli cell apoptosis. We observed that upon knocking down Ppm1g in rat testes, the function of the blood testis barrier was compromised, and the localization of α-catenin and β-catenin became aberrant. Further investigation in rat Sertoli cells revealed that after Ppm1g knockdown, the level of phosphorylated α-catenin increased, and it failed to properly aggregate at the cell membrane; instead, it was mislocalized to the cytoplasm. The actin to which catenin is attached also exhibited a disordered arrangement in the absence of PPM1G. Additionally, through RNA sequencing and bioinformatics analysis, we identified genes associated with Sertoli cell dysfunction induced by Ppm1g knockdown and identified a set of genes involved in regulating intercellular junctions. Subsequent validation revealed that after Ppm1g knockdown, the expression of the junction-related protein JAM2 was reduced, and Sertoli cells underwent apoptosis. Overall, we identified a gene, Ppm1g, which may be involved in maintaining the normal function of the blood-testis barrier and influencing the survival of Sertoli cells by regulating apoptotic pathways.