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

作者：Chung Jean Ju; Navarro Betsy; Krapivinsky Grigory; Krapivinsky Luba; Clapham David E^*

来源：Nature Communications, 2011, 2(1): 153.

DOI：10.1038/ncomms1153

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 a subunits. In addition to the pore-forming proteins, the sperm Ca(2+) channel contains auxiliary subunits, CATSPER beta and CATSPER gamma. Here, we identify the Tmem146 gene product as a novel subunit, CATSPER delta, required for CATSPER channel function. We find that mice lacking the sperm tail-specific CATSPERd are infertile and their spermatozoa lack both Ca(2+) current and hyperactivated motility. We show that CATSPERd is an essential element of the CATSPER channel complex and propose that CATSPERd is required for proper CATSPER channel assembly and/or transport.

• 出版日期2011-1