The fusion of sperm and egg lead to the combination of the father's and mother's genetic information to create a new individual. In humans, as in all mammals, sperm must reach the egg, penetrate its protective coat, fuse with the oocyte membrane, and deliver its genetic material. Ion channels in the sperm mediate many of these steps. We have identified four ion channels that are in sperm but not other tissues. CatSpers (Cation channel of Sperm) are six transmembrane-spanning ion channel proteins localized primarily to the tail of mature sperm (Ren et al, 2001). CatSper1 is an ion channel that triggers calcium-influx into the principal piece of the sperm tail. Male mice homozygous for null-mutations in the CatSper1 gene are 100% infertile, but otherwise are completely normal. Sperm from mice genetically engineered to lack the functional CatSper1 gene show a significant reduction in motility and are incapable of penetrating through the outer coat of an egg. ? We have identified two new sperm-specific proteins, CatSper3 and CatSper4 that are localized to the sperm tail. Experiments are proposed that will delineate the function of these novel ion channels and reveal their role in sperm function. Understanding these proteins will increase our understanding of fertilization and shed light on both some causes of male infertility as well as provide new targets for contraceptive agents. ? ?
|Chung, Jean-Ju; Navarro, Betsy; Krapivinsky, Grigory et al. (2011) A novel gene required for male fertility and functional CATSPER channel formation in spermatozoa. Nat Commun 2:153|
|Cai, Xinjiang; Clapham, David E (2008) Evolutionary genomics reveals lineage-specific gene loss and rapid evolution of a sperm-specific ion channel complex: CatSpers and CatSperbeta. PLoS One 3:e3569|
|Navarro, Betsy; Kirichok, Yuriy; Clapham, David E (2007) KSper, a pH-sensitive K+ current that controls sperm membrane potential. Proc Natl Acad Sci U S A 104:7688-92|
|Qi, Huayu; Moran, Magdalene M; Navarro, Betsy et al. (2007) All four CatSper ion channel proteins are required for male fertility and sperm cell hyperactivated motility. Proc Natl Acad Sci U S A 104:1219-23|