Calcium pumps in health and disease.

  title={Calcium pumps in health and disease.},
  author={Marisa Brini and Ernesto Carafoli},
  journal={Physiological reviews},
  volume={89 4},
Ca2+-ATPases (pumps) are key actors in the regulation of Ca2+ in eukaryotic cells and are thus essential to the correct functioning of the cell machinery. They have high affinity for Ca2+ and can efficiently regulate it down to very low concentration levels. Two of the pumps have been known for decades (the SERCA and PMCA pumps); one (the SPCA pump) has only become known recently. Each pump is the product of a multigene family, the number of isoforms being further increased by alternative… 

Calcium pumps: why so many?

Most of the pump defects described so far are genetic and produce subtler, often tissue and isoform specific, disturbances that affect individual components of the Ca( 2+)-controlling and/or processing machinery, compellingly indicating a specialized role for each Ca(2+) pump type and/ or isoform.

The plasma membrane calcium pump in health and disease

The PMCAs are essential to the regulation of cellular Ca2+, but the all‐important Ca2+ signal is ambivalent: defects in its control generate various pathologies, the most thoroughly studied being those of genetic origin.

The plasma membrane calcium pumps: focus on the role in (neuro)pathology.

Regulation of Cell Calcium and Role of Plasma Membrane Calcium ATPases.

Role of ATPases in Disease Processes

The properties and functioning of the calcium pumps are discussed and its association with different malfunction and diseases are highlighted, which might be effective in using the calcium pump targets as therapeutic targets for drug development in the near future.

The Plasma Membrane Calcium Pump: New Ways to Look at an Old Enzyme

The concept is now emerging that the global control of cell Ca2+ may not be the main function of the pump; in some cell types, it could even be irrelevant.

The Plasma Membrane Calcium ATPases and Their Role as Major New Players in Human Disease.

Evidence of the variety of tissue-specific functions of PMCAs is brought together and the roles these genes play in regulating normal physiological functions and the considerable impact the genes have on human disease are highlighted.

Calcium-ATPases: Gene disorders and dysregulation in cancer.

A Role for SERCA Pumps in the Neurobiology of Neuropsychiatric and Neurodegenerative Disorders.

Current evidence suggesting a role for SERCA in the neurobiology of neuropsychiatric and neurodegenerative disorders is summarized, highlighting the importance of this pump in brain physiology and pathophysiology.



The role of plasma membrane Ca2+ pumps (PMCAs) in pathologies of mammalian cells.

This review summarizes the results of recent analysis of the PMCA dysregulation in diseased cells or model systems of pathological conditions, including both acute disorders like hypoxia/ischemia and seizure, and slowly progressing dysfunctions like Alzheimer's disease, hypertension, diabetes and aging.

Role of alternative splicing in generating isoform diversity among plasma membrane calcium pumps.

The identification of mice carrying PMCA mutations that lead to diseases such as hearing loss and ataxia, as well as the corresponding phenotypes of genetically engineered PMCA "knockout" mice further support the concept of specific, nonredundant roles for each Ca( 2+) pump isoform in cellular Ca(2+) regulation.

Physiological implications of the interaction between the plasma membrane calcium pump and nNOS

The role of PMCA is highlighted as a modulator of signal transduction pathways and in particular the role of isoform 4 in the regulation of the nitric oxide signalling pathway is highlighted.

The regulatory function of plasma-membrane Ca(2+)-ATPase (PMCA) in the heart.

Recent advances that support a key role for PMCA4 in modulating the nitric oxide signalling pathway in the heart are discussed.

Phenotypes of SERCA and PMCA knockout mice.

Biogenesis: Plasma membrane calcium ATPase: 15 years of work on the purified enzyme 1

  • E. Carafoli
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1994
The analogy of the regulation mechanisms of the two pumps is heightened by the finding that phosphorylation of the calmodulin binding domain by protein kinase C removes its autoinhibiting function, as other kinases do in the case of phospholamban.

Calcium signaling in the cell nucleus

  • L. SantellaE. Carafoli
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1997
A final picture on the traffic of Ca2+ in and out of the nucleus must also include theCa2+ pump as well as the InsP3 and cyclic ADP ribose‐modulated Ca2+, which has been documented in the envelope.

When calcium goes wrong: genetic alterations of a ubiquitous signaling route

The number of known genetic diseases that can be attributed to defects in proteins directly involved in Ca2+ homeostasis is limited to few examples, and paucity in contrast with the wide molecular repertoire may depend on the extreme severity of the phenotype.

A Comparative Functional Analysis of Plasma Membrane Ca2+ Pump Isoforms in Intact Cells*

The results indicate that the availability of calmodulin may not be critical for the modulation of PMCA pumps in vivo and thatPMCA4CII(4a) was as effective as PMCA4CI(4b), even if its affinity for calmodoxin is much lower.

Abnormal intracellular ca(2+)homeostasis and disease.

Disease-causing mutations or abnormalities provide new insights into the cell biology of the various Ca(2+)transporters, which in vitro seem to induce trivial functional alterations, and often lead to a plethora of diseases.