The serine/threonine phosphatase (PP1) isoform PP12, predominantly expressed in the testis, is a key enzyme in spermatozoa. High PP12 catalytic activity holds motility in check in immature spermatozoa. Inhibition of PP12 causes motility initiation in immature spermatozoa and motility stimulation and changes in flagellar beat parameters in mature spermatozoa. The PP12 isoform is present in all mammalian spermatozoa studied: mouse, rat, hamster, bovine, non-human primate and man. We have now identified at least four of its regulatory proteins that regulate distinct pools of PP12 within spermatozoa. Our studies provide new insights into biochemical mechanisms underlying development and regulation of sperm motility. We hypothesize that changes in sperm PP12 activity as a result of phosphorylation and reversible binding of the regulatory proteins to the catalytic subunit are critical in the development and regulation of motility and the ability of sperm to fertilize eggs. Targeted disruption of the Ppp1cc gene, which encodes the PP11 or PP12 isoforms, causes male infertility in mice as a result of impaired spermiogenesis. Our observations suggest that, in addition to motility, the protein phosphatase PP12 might play an isoform-specific function in the development of specialized flagellar structures of mammalian spermatozoa.

Keywords: protein phosphatase, epididymis, sperm motility, spermatogenesis

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