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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Jimenez, Tamara Sánchez, Gladis Mcdermott, Jeffrey P. Blanco, Gustavo |
| Description | Author Affiliation: Jimenez T ( Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.); |
| Abstract | Regulation of ion balance in spermatozoa has been shown to be essential for sperm motility and fertility. Control of intracellular ion levels requires the function of distinct ion-transport mechanisms at the cell plasma membrane. Active Na(+) and K(+) exchange in sperm is under the control of the Na,K-ATPase. Two molecular variants of the catalytic subunit of the Na,K-ATPase, 1 and 4, coexist in sperm. These isoforms exhibit different biochemical properties; however, their function in sperm fertility is unknown. In this work, we show that Na,K-ATPase 4 is essential for sperm fertility. Knockout male mice lacking 4 are completely sterile and spermatozoa from these mice are unable of fertilizing eggs in vitro. Furthermore, 4 deletion results in severe reduction in sperm motility and hyperactivation typical of sperm capacitation. In addition, absence of 4 causes a characteristic bend in the sperm flagellum, indicative of abnormal sperm ion regulation. Accordingly, 4-null sperm present increased intracellular Na(+) and cell plasma membrane depolarization. These results are unique in demonstrating the absolute requirement of 4 for sperm fertility. Moreover, the inability of 1 to compensate for 4 suggests that 4 is the Na,K-ATPase- isoform directly involved in sperm fertility. Our findings show 4 as an attractive target for male contraception and open the possibility for the potential use of this Na,K-ATPase isoform as a biomarker for male fertility. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 2 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Protein Isoforms Sodium-Potassium-Exchanging ATPase Chemistry Spermatozoa Pathology Animals Biological Markers Catalysis Cell Membrane Metabolism Membrane Potentials Mice Mice, Knockout Models, Genetic Sperm Motility Research Support, N.I.H., Extramural Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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