During mammalian fertilization, Ca2+ signaling plays a central role in sperm capacitation and motility to the fusion between sperm and egg1. Several Ca2+-permeable ion channel proteins have been characterized in mammalian sperm. However, only the four mammalian CatSper members (CatSpers 1-4) are restrictively expressed in the testis and are clearly shown to be required for male fertility2.
CatSper channels are named after the first putative cation channel of sperm3. CatSper4 contains a single ion transport domain comprised of 6 transmembrane spanning regions, where the fourth transmembrane region resembles a voltage sensor and a pore forming region lies between transmembrane regions 5 and 6. The pore contains the consensus sequence T×D×W indicative of a probable Ca2+ selective channel4. The four CatSper proteins are primarily localized to the plasma membrane of the distal portion of the sperm tail and presumably form a heterotetrameric, pH- and voltage-dependent Ca2+-permeable channel 5.
CatSper 4 is highly expressed in testis and expressed at low levels in placenta and lung6.
Male mice deficient in any of the four CatSper are completely sterile but exhibit no other apparent abnormality. The major phenotypes of the null sperm are a lack of hyperactivated motility, a gradual loss of motility after isolation, and an inability to penetrate zona-intact eggs7.
