Protein phosphatase I complexes modulate sperm motility and present novel targents for male infertility

摘要

Infertility is a growing concern in modern society, with 30% of cases being due to male factors, namely reduced sperm concentration, decreased motility and abnormal morphology. Sperm cells are highly compartmentalized, almost devoid of transcription and translation consequently processes such as protein phosphorylation provide a key general mechanism for regulating vital cellular functions, more so than for undifferentiated cells. Reversible protein phosphorylation is the principal mechanism regulating most physiological processes in eukaryotic cells. To date, hundreds of protein kinases have been identified, but significantly fewer phosphatases (PPs) are responsible for counteracting their action. This discrepancy can be explained in part by the mechanism used to control phosphatase activity, which is based on regulatory interacting proteins. This is particularly true for PPI, a major serine/threonine-PP, for which > 200 interactors (PPI interacting proteins-PIPs) have been indentified that control its activity, subcellular location and substrate specificity. For PPI, several isoforms have been described, among them PPIgamma2, a testis/sperm-enriched PPI isoform. Recent findings support our hypothesis that PPIgamma2 is involved in the regulation of sperm motility. This review summarizes the known sperm-specific PPI-PIPs, involved in the acquisition of mammalian sperm motility. The complexes that PPI routinely forms with different proteins are addressed and the role of PPI /A-kinase anchoring protein complexes in sperm motility is considered. Furthermore, the potential relevance of targeting PPI-PIPs complexes to infertility diagnostics and therapeutics as well as to male contraception is also discussed.