Plasma membrane Ca2+ ATPase 4 is required for sperm motility and male fertility.
Calcium and Ca(2+)-dependent signals play a crucial role in sperm motility and mammalian fertilization, but the molecules and mechanisms underlying these Ca(2+)-dependent pathways are incompletely understood. Here we show that homozygous male mice with a targeted gene deletion of isoform 4 of the plasma membrane calcium/calmodulin-dependent calcium ATPase (PMCA), which is highly enriched in the sperm tail, are infertile due to severely impaired sperm motility. Furthermore, the PMCA inhibitor 5-(and-6)-carboxyeosin diacetate succinimidyl ester reduced sperm motility in wild-type animals, thus mimicking the effects of PMCA4 deficiency on sperm motility and supporting the hypothesis of a pivotal role of the PMCA4 on the regulation of sperm function and intracellular Ca(2+) levels.
Schuh
Kai
K
Institute for Clinical Biochemistry and Pathobiochemistry, University of Wuerzburg, Josef-Schneider-Strasse 2, D-97080 Wuerzburg, Germany. schuh_k@klinik.uni-wuerzburg.de
Cartwright
Elizabeth J
EJ
Jankevics
Eriks
E
Bundschu
Karin
K
Liebermann
Jürgen
J
Williams
Judith C
JC
Armesilla
Angel L
AL
Emerson
Michael
M
Oceandy
Delvac
D
Knobeloch
Klaus-Peter
KP
Neyses
Ludwig
L
D017398:Alternative Splicing; D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000096:biosynthesis*; D027682:Cation Transport Proteins; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D005298:Fertility; D005307:Fertilization in Vitro; D005452:Fluoresceins / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000494:pharmacology; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D008969:Molecular Sequence Data; D053499:Plasma Membrane Calcium-Transporting ATPases; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D051381:Rats; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013081:Sperm Motility; D013388:Succinimides / Q000494:pharmacology; D013737:Testis / Q000378:metabolism; D013997:Time Factors
C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D027682:Cation Transport Proteins; D018076:DNA, Complementary; D005452:Fluoresceins; D005456:Fluorescent Dyes; D020033:Protein Isoforms; D013388:Succinimides; D053499:Plasma Membrane Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium