The plasma membrane calcium pump in health and disease
- PMID: 23413890
- DOI: 10.1111/febs.12193
The plasma membrane calcium pump in health and disease
Abstract
The Ca(2+) ATPases of the plasma membrane (PMCA pumps) export Ca(2+) from all eukaryotic cells. In mammals they are the products of four separate genes. PMCA types 1 and 4 are distributed ubiquitously; PMCA types 2 and 3 are restricted to some tissues, the most important being the nervous system. Alternative splicing at two sites greatly increases the number of pump isoforms. The two ubiquitous isoforms are no longer considered as only housekeeping pumps as they also perform tissue-specific functions. The PMCAs are classical P-type pumps, their reaction cycle repeating that of all other pumps of the family. Their 3D structure has not been solved, but molecular modeling on SERCA pump templates shows the essential structural pattern of the latter. PMCAs are regulated by calmodulin, which interacts with high affinity with their cytosolic C-terminal tail. A second calmodulin-binding domain with lower affinity is present in some splicing variants of the pump. The PMCAs are essential to the regulation of cellular Ca(2+), but the all-important Ca(2+) signal is ambivalent: defects in its control generate various pathologies, the most thoroughly studied being those of genetic origin. Genetic defects of PMCA function produce disease phenotypes: the best characterized is a form of deafness in mice and in humans linked to PMCA2 mutations. A cerebellar X-linked human ataxia has recently been found to be caused by a mutation in the calmodulin-binding domain of PMCA3.
Keywords: PMCA mutations; cerebellar ataxia; genetic deafness; plasma membrane Ca2+ pumps; pump isoforms.
© 2013 The Authors Journal compilation © 2013 FEBS.
Similar articles
-
The PMCA pumps in genetically determined neuronal pathologies.Neurosci Lett. 2018 Jan 10;663:2-11. doi: 10.1016/j.neulet.2017.11.005. Epub 2017 Nov 17. Neurosci Lett. 2018. PMID: 29155350 Review.
-
Role of alternative splicing in generating isoform diversity among plasma membrane calcium pumps.Physiol Rev. 2001 Jan;81(1):21-50. doi: 10.1152/physrev.2001.81.1.21. Physiol Rev. 2001. PMID: 11152753 Review.
-
Plasma membrane calcium ATPases and related disorders.Int J Biochem Cell Biol. 2013 Mar;45(3):753-62. doi: 10.1016/j.biocel.2012.09.016. Epub 2012 Oct 4. Int J Biochem Cell Biol. 2013. PMID: 23041476 Review.
-
The plasma membrane calcium pump in the hearing process: physiology and pathology.Sci China Life Sci. 2011 Aug;54(8):686-90. doi: 10.1007/s11427-011-4200-z. Epub 2011 Jul 24. Sci China Life Sci. 2011. PMID: 21786191 Review.
-
The plasma membrane calcium pumps: focus on the role in (neuro)pathology.Biochem Biophys Res Commun. 2017 Feb 19;483(4):1116-1124. doi: 10.1016/j.bbrc.2016.07.117. Epub 2016 Jul 29. Biochem Biophys Res Commun. 2017. PMID: 27480928 Review.
Cited by
-
Specific Activation of the Plant P-type Plasma Membrane H+-ATPase by Lysophospholipids Depends on the Autoinhibitory N- and C-terminal Domains.J Biol Chem. 2015 Jun 26;290(26):16281-91. doi: 10.1074/jbc.M114.617746. Epub 2015 May 13. J Biol Chem. 2015. PMID: 25971968 Free PMC article.
-
Structural Changes of Sarco/Endoplasmic Reticulum Ca2+-ATPase Induced by Rutin Arachidonate: A Molecular Dynamics Study.Biomolecules. 2020 Feb 1;10(2):214. doi: 10.3390/biom10020214. Biomolecules. 2020. PMID: 32024167 Free PMC article.
-
Molecular aspects of intestinal calcium absorption.World J Gastroenterol. 2015 Jun 21;21(23):7142-54. doi: 10.3748/wjg.v21.i23.7142. World J Gastroenterol. 2015. PMID: 26109800 Free PMC article. Review.
-
Intracellular calcium links milk stasis to lysosome-dependent cell death during early mammary gland involution.Cell Mol Life Sci. 2024 Jan 12;81(1):29. doi: 10.1007/s00018-023-05044-8. Cell Mol Life Sci. 2024. PMID: 38212474 Free PMC article.
-
A link between plasma membrane calcium ATPase 2 (PMCA2), estrogen and estrogen receptor α signaling in mechanical pain.Sci Rep. 2018 Nov 22;8(1):17260. doi: 10.1038/s41598-018-35263-0. Sci Rep. 2018. PMID: 30467368 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous
