title: A novel gene required for male fertility and functional CATSPER channel formation in spermatozoa.
abstract: Calcium signalling is critical for successful fertilization. In spermatozoa, capacitation, hyperactivation of motility and the acrosome reaction are all mediated by increases in intracellular Ca(2+). Cation channels of sperm proteins (CATSPERS1-4) form an alkalinization-activated Ca(2+)-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 Ca(2+)-selective pore, in analogy with other six-transmembrane ion channel α subunits. In addition to the pore-forming proteins, the sperm Ca(2+) 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 Ca(2+) 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.
authors.affiliation: 1] Howard Hughes Medical Institute, Manton Center for Orphan Disease, Children's Hospital, Boston, Massachusetts 02115, USA.. [2] Department of Neurobiology, Harvard Medical School, Enders 1309, 320 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Jean-Ju
authors.initials: JJ
authors.lastname: Chung
authors.forename: Betsy
authors.initials: B
authors.lastname: Navarro
authors.forename: Grigory
authors.initials: G
authors.lastname: Krapivinsky
authors.forename: Luba
authors.initials: L
authors.lastname: Krapivinsky
authors.forename: David E
authors.initials: DE
authors.lastname: Clapham