Deletion of type II alpha regulatory subunit delocalizes protein kinase A in mouse sperm without affecting motility or fertilization

Cyclic AMP stimulates sperm motility in a variety of mammalian species, but the molecular details of the intracellular signaling pathway responsible f or this effect are unclear. The type II alpha isoform of protein kinase A ( PKA) is induced late in spermatogenesis and is thought to localize PRA to t he flagellar apparatus where it binds cAMP and stimulates motility. A targe ted disruption of the type II alpha regulatory subunit (RII alpha) gene all owed us to examine the role of PKA localization in sperm motility and ferti lity. In wild type sperm, PKA is found primarily in the detergent-resistant particulate fraction and localizes to the mitochondrial-containing midpiec e and the principal piece. In mutant sperm, there is a compensatory increas e in RI alpha protein and a dramatic relocalization of PKA such that the ma jority of the holoenzyme now appears in the soluble fraction and colocalize s with the cytoplasmic droplet. Unexpectedly the RII alpha mutant mice are fertile and have no significant changes in sperm motility. Our results demo nstrate that the highly localized pattern of PKA seen in mature sperm is no t essential for motility or fertilization.