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Ankyrin-B Coordinates the Na/K ATPase, Na/Ca Exchanger, and InsP3 Receptor in a Cardiac T-Tubule/SR Microdomain
Open accessAbstract
We report identification of an ankyrin-B-based macromolecular complex of Na/K ATPase (alpha 1 and alpha 2 isoforms), Na/Ca exchanger 1, and InsP3 receptor that is localized in cardiomyocyte T-tubules in discrete microdomains distinct from classic dihydropyridine receptor/ryanodine receptor "dyads." E1425G mutation of ankyrin-B, which causes human cardiac arrhythmia, also blocks binding of ankyrin-B to all three components of the complex. The ankyrin-B complex is markedly reduced in adult ankyrin-B(+/-) cardiomyocytes, which may explain elevated [Ca2+]i transients in these cells. Thus, loss of the ankyrin-B complex provides a molecular basis for cardiac arrhythmia in humans and mice. T-tubule-associated ankyrin-B, Na/Ca exchanger, and Na/K ATPase are not present in skeletal muscle, where ankyrin-B is expressed at 10-fold lower levels than in heart. Ankyrin-B also is not abundantly expressed in smooth muscle. We propose that the ankyrin-B-based complex is a specialized adaptation of cardiomyocytes with a role for cytosolic Ca2+ modulation.
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Cites
Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death
Mohler, P. J., Schott, J.-J., Gramolini, A. O., Dilly, K. W., Guatimosim, S., duBell, W. H., Song, L.-S., Haurogné, K., Kyndt, F., Ali, M. E., et al. (2003) · Nature · doi:10.1038/nature01335 · Cited by 957
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Cited by
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Lytton, J. (2007) · Biochemical Journal · doi:10.1042/bj20070619 · Cited by 408
ter Keurs, H. E. D. J., & Boyden, P. A. (2007) · Physiological Reviews · doi:10.1152/physrev.00011.2006 · Cited by 356
Molecular basis for PP2A regulatory subunit B56α targeting in cardiomyocytes
Bhasin, N., Cunha, S. R., Mudannayake, M., Gigena, M. S., Rogers, T. B., & Mohler, P. J. (2007) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00059.2007 · Cited by 96
Self-citationCUNHA, S., & MOHLER, P. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.03.018 · Cited by 65
Self-citationThe Na(+)/K(+) pump dominates control of glycolysis in hippocampal dentate granule cells
Meyer, D. J., Díaz-García, C. M., Nathwani, N., Rahman, M., & Yellen, G. (2022) · eLife · doi:10.7554/elife.81645 · Cited by 40
Metadata
- Authors
- Mohler, P. J., Davis, J. Q., & Bennett, V.
- Venue
- PLoS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2005-11-29
- Volume
- 3
- Issue
- 12
- Pages
- e423
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- OpenAlex
- W1971203163
- Cited by
- 245
- References
- 1
- FWCI
- 10.82
- Type
- journal article
- Language
- en
- Open access
- gold
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- Mohler, P. J., Davis, J. Q., & Bennett, V. (2005). Ankyrin-B Coordinates the Na/K ATPase, Na/Ca Exchanger, and InsP3 Receptor in a Cardiac T-Tubule/SR Microdomain. PLoS Biology. https://doi.org/10.1371/journal.pbio.0030423
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