Insights into sperm cell motility signaling through sNHE and the CatSpers

Successful natural reproduction normally requires vigorously motile spermatozoa. Using a signal peptide trapping strategy, we identified two new genes, a putative sperm Na+/H+ exchanger (sNHE) and the putative cation channel CatSper2, with unique and essential roles in sperm motility. Disruption of the sNHE or CatSper2 genes in mice caused male infertility due to immotile spermatozoa or failed motility hyperactivation, respectively, without other apparent abnormalities. The immotility phenotype of the sNHE null spermatozoa appears to result from an intimate association of sNHE and the atypical adenylyl cyclase (sAC), while a failure of calcium entry requiring an apparent CatSper1 and -2 heteromeric ion channel correlates with a hyperactivation defect in these null animals. The specific expression of sNHE and the CatSpers in spermatozoa and their required function in cell motility make them excellent potential targets for the development of novel male contraceptives.