title: 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.
authors: Department of Comparative Biomedicine and Food Science, University of Padova, Italy.
authors: Marisa
authors: M
authors: Brini
authors: Tito
authors: T
authors: Calì
authors: Denis
authors: D
authors: Ottolini
authors: Ernesto
authors: E
authors: Carafoli
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000201:enzymology*; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D051379:Mice; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics* / Q000378:metabolism
chemical_list: D053499:Plasma Membrane Calcium-Transporting ATPases
keywords: PMCA mutations; cerebellar ataxia; genetic deafness; plasma membrane Ca2+ pumps; pump isoforms