A sperm ion channel required for sperm motility and male fertility.
Calcium and cyclic nucleotides have crucial roles in mammalian fertilization, but the molecules comprising the Ca2+-permeation pathway in sperm motility are poorly understood. Here we describe a putative sperm cation channel, CatSper, whose amino-acid sequence most closely resembles a single, six-transmembrane-spanning repeat of the voltage-dependent Ca2+-channel four-repeat structure. CatSper is located specifically in the principal piece of the sperm tail. Targeted disruption of the gene results in male sterility in otherwise normal mice. Sperm motility is decreased markedly in CatSper-/- mice, and CatSper-/- sperm are unable to fertilize intact eggs. In addition, the cyclic-AMP-induced Ca2+ influx is abolished in the sperm of mutant mice. CatSper is thus vital to cAMP-mediated Ca2+ influx in sperm, sperm motility and fertilization. CatSper represents an excellent target for non-hormonal contraceptives for both men and women.
Ren
D
D
Howard Hughes Medical Institute, Children's Hospital, Harvard Medical School, Enders 1309, 320 Longwood Avenue, Boston, Massachusetts 02115, USA.
Navarro
B
B
Perez
G
G
Jackson
A C
AC
Hsu
S
S
Shi
Q
Q
Tilly
J L
JL
Clapham
D E
DE
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000502:physiology; D004594:Electrophysiology; D005260:Female; D005298:Fertility / Q000235:genetics / Q000502:physiology*; D005306:Fertilization; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D013081:Sperm Motility / Q000502:physiology*; D013082:Sperm Tail / Q000378:metabolism; D013094:Spermatozoa / Q000737:chemistry / Q000502:physiology*; D013234:Stem Cells
C438823:CATSPER1 protein, human; D015220:Calcium Channels; D000242:Cyclic AMP; D002118:Calcium