title: Plasma membrane calcium ATPases and related disorders.
abstract: The plasma membrane Ca(2+) ATPases (PMCA pumps) cooperate with other transport systems in the plasma membrane and in the organelles in the regulation of cell Ca(2+). They have high Ca(2+) affinity and are thus the fine tuners of cytosolic Ca(2+). They belong to the superfamily of P-type ATPases: their four basic isoforms share the essential properties of the reaction cycle and the general membrane topography motif of 10 transmembrane domains and three large cytosolic units. However they also differ in other important properties, e.g., tissue distribution and regulatory mechanisms. Their chief regulator is calmodulin, that removes their C-terminal cytosolic tail from autoinhibitory binding sites next to the active site of the pump, restoring activity. The number of pump isoforms is increased to over 30 by alternative splicing of the transcripts at a N-terminal site (site A) and at site C within the C-terminal calmodulin binding domain: the splice variants are tissue specific and developmentally regulated. The importance of PMCAs in the maintenance of cellular Ca(2+) homeostasis is underlined by the disease phenotypes, genetic or acquired, caused by their malfunction. Non-genetic PMCA deficiencies have long been considered possible causative factors in disease conditions as important as cancer, hypertension, or neurodegeneration. Those of genetic origin are better characterized: some have now been discovered in humans as well. They concern all four PMCA isoforms, and range from cardiac dysfunctions, to deafness, to hypertension, to cerebellar ataxia.
authors.affiliation: Venetian Institute of Molecular Medicine, University of Padova, Padua, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Giacomello
authors.forename: Agnese
authors.initials: A
authors.lastname: De Mario
authors.forename: Chiara
authors.initials: C
authors.lastname: Scarlatti
authors.forename: Simona
authors.initials: S
authors.lastname: Primerano
authors.forename: Ernesto
authors.initials: E
authors.lastname: Carafoli
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000235:genetics*; D002147:Calmodulin / Q000378:metabolism; D020134:Catalytic Domain; D002462:Cell Membrane / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D020033:Protein Isoforms / Q000235:genetics
chemical_list: D002147:Calmodulin; D020033:Protein Isoforms; D053499:Plasma Membrane Calcium-Transporting ATPases; D002118:Calcium