Chung, Jean-JuNavarro, BetsyKrapivinsky, GrigoryKrapivinsky, LubaClapham, David2014-05-062014Chung, Jean-Ju, Betsy Navarro, Grigory Krapivinsky, Luba Krapivinsky, and David E. Clapham. 2014. “A Novel Gene Required for Male Fertility and Functional CATSPER Channel Formation in Spermatozoa.” Nature communications 2 (1): 153. doi:10.1038/ncomms1153. http://dx.doi.org/10.1038/ncomms1153.2041-1723http://nrs.harvard.edu/urn-3:HUL.InstRepos:12152829Summary Calcium signaling is critical for successful fertilization. In spermatozoa, capacitation, hyperactivation of motility, and the acrosome reaction are all mediated by increases in intracellular Ca2+. Cation channels of sperm proteins (CATSPERS1-4) form an alkalinization-activated Ca2+-selective channel required for the hyperactivated motility of spermatozoa and male fertility. Each of the CatSper1-4 genes encodes a subunit of a tetramer surrounding a Ca2+-selective pore, in analogy with other six-transmembrane ion channel α subunits. In addition to the pore-forming proteins, the sperm Ca2+ channel contains auxiliary subunits, CATSPERβ and CATSPERγ. Here, we identify the Tmem146 gene product as a novel subunit, CATSPERδ, required for CATSPER channel function. We find that mice lacking the sperm tail-specific CATSPERδ are infertile and their spermatozoa lack both Ca2+ current and hyperactivated motility. We show that CATSPERδ is an essential element of the CATSPER channel complex and propose that CATSPERδ is required for proper CATSPER channel assembly and/or transport.en-USJournal Article2014-05-0610.1038/ncomms1153