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

JJL Chung, B Navarro, G Krapivinsky, L Krapivinsky… - Biophysical …, 2011 - cell.com
JJL Chung, B Navarro, G Krapivinsky, L Krapivinsky, DE Clapham
Biophysical Journal, 2011cell.com
Calcium (Ca2+) signaling is critical for successful fertilization. In spermatozoa, capacitation,
hyperactivation of motility, and the acrosome reaction are mediated by changes in the
intracellular Ca2+. Cation channels of sperm (CatSpers1-4) are alkalinization-activated
Ca2+-selective ion channels controlling hyperactivated motility of spermatozoa and male
fertility. CatSpers form a heteromeric complex with each of the CatSpers1-4 surrounding a
Ca2+-selective pore, in analogy with other six-transmembrane (6TM) ion channel alpha …
Calcium (Ca2+) signaling is critical for successful fertilization. In spermatozoa, capacitation, hyperactivation of motility, and the acrosome reaction are mediated by changes in the intracellular Ca2+. Cation channels of sperm (CatSpers1-4) are alkalinization-activated Ca2+-selective ion channels controlling hyperactivated motility of spermatozoa and male fertility. CatSpers form a heteromeric complex with each of the CatSpers1-4 surrounding a Ca2+-selective pore, in analogy with other six-transmembrane (6TM) ion channel alpha subunits. In addition to the pore-forming proteins, the sperm Ca2+ channel contains auxiliary subunits, CatSper beta and CatSper gamma. Here, we identify the Tmem146 gene product as another novel CatSper accessory subunit, CatSper delta. We find that mice lacking the sperm tail-specific CatSper delta are infertile and their spermatozoa lack both CatSper current and hyperactivated motility. We show that CatSper delta has a central role in CatSper channel complex stability during spermatogenesis, providing new insight into the function of auxiliary subunits and the mechanism of CatSper channel complex assembly.
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