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A novel gene required for male fertility and functional CATSPER channel formation in spermatozoa.

Nature communications | Jan 11, 2011

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.

Pubmed ID: 21224844 RIS Download

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Associated grants

  • Agency: Howard Hughes Medical Institute, Id: P30 HD018655
  • Agency: NICHD NIH HHS, Id: R01 HD045339
  • Agency: NICHD NIH HHS, Id: U01 HD045857
  • Agency: NICHD NIH HHS, Id:

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