Phosphoprotein phosphatase 1 complexes in spermatogenesis.

The major post-translational modification in eukaryotes is protein phosphorylation which mediates responses to signals in a myriad of cellular processes. Not surprisingly, many steps in spermatogenesis involve the concerted action of the protein (de)phosphorylation key players, kinases and phosphatases. Phosphoprotein phosphatase 1 catalytic subunit (PPP1C), an evolutionarily conserved Ser/Thr-protein phosphatase, catalyzes the majority of eukaryotic protein dephosphorylation reactions. Three genes, PPP1CA, PPP1CB and PPP1CC, encode four PPP1C isoforms, PPP1CA, PPP1CB, PPP1CC1, and PPP1CC2. After transcription, PPP1CC undergoes tissue-specific splicing, originating a ubiquitously expressed isoform, PPP1CC1 and a testis-enriched and sperm-specific isoform, PPP1CC2 which is essential for completion of spermatogenesis. Highly similar PPP1C isoforms - PPP1CA and PPP1CB - are capable of compensating the loss of Ppp1cc in every tissue except in testis. PPP1C cellular functions depend on the complexes it forms with PPP1C Interacting Proteins (PIPs), which together with the different catalytic subunits, account for PPP1C specificity. This review will focus on the role of the major serine/threonine phosphatase - PPP1C and its holoenzymes in spermatogenesis. Furthermore, current challenges on the protein phosphatases field as targets to male contraception will be addressed.