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. ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD045339-03
Application #
6986823
Study Section
Reproductive Biology Study Section (REB)
Program Officer
Rankin, Tracy L
Project Start
2004-01-01
Project End
2008-12-31
Budget Start
2006-01-01
Budget End
2006-12-31
Support Year
3
Fiscal Year
2006
Total Cost
$320,340
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
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