Kwang-Hyun Park, Byung-Ju Kim, John Kang
May 17, 2011
Prostate-derived vesicles provide sperm with calcium signaling proteins required for progesterone-induced motility. Delivering Sperm a Toolkit Progesterone stimulates complex calcium signals in human sperm that have been implicated in enhancing their motility. Noting that sperm are structurally simple cells with a minimal complement of organelles, Park et al. explored the possibility that prostasomes (small vesicles secreted by the prostate) might deliver a “calcium toolkit” to sperm to enable these complex calcium responses. Analyses of sperm isolated before prostasome exposure revealed that, indeed, fusion with prostasomes led to the acquisition in sperm of various proteins implicated in calcium signaling and enabled the progesterone-dependent mobilization of calcium from internal stores. Moreover, prostasomal proteins promoted progesterone-dependent sperm motility and enhanced the ability of mouse sperm to fertilize ova. Progesterone-induced calcium ion (Ca2+) signals in the neck region of sperm play a pivotal role in promoting sperm motility. Here, we show that a long-lasting Ca2+ signal required for sperm motility in response to progesterone depends on their pH-dependent fusion with prostasomes, which are small vesicles secreted by the prostate. We found that prostasome fusion led to the transfer of progesterone receptors, cyclic adenosine diphosphoribose (cADPR)–synthesizing enzymes, ryanodine receptors (RyRs), and other Ca2+ signaling tools from prostasomes to the sperm neck. Progesterone-induced sperm motility relied on cADPR-mediated Ca2+ mobilization through RyR located on acidic Ca2+ stores, followed by Ca2+ entry through store-operated channels. Treatment of prostasome-fused sperm with a cADPR antagonist or fusion with prostasomes in which type 2 RyR was depleted resulted in low fertilization rates, reduced sperm motility, or both. Thus, we conclude that sperm motility depends on the acquisition of Ca2+ signaling tools from prostasomes.