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1536373 
Journal Article 
The plasma membrane Ca2+ ATPase of animal cells: Structure, function and regulation 
Di Leva, F; Domi, T; Fedrizzi, L; Lim, D; Carafoli, E 
2008 
Yes 
Archives of Biochemistry and Biophysics
ISSN: 0003-9861
EISSN: 1096-0384 
476 
1 
65-74 
18328800 
WOS:000258165700008 
Most important processes in cell life are regulated by
calcium (Ca2+). A number of mechanisms have thus been developed to maintain the concentration of
free Ca2+ inside cells at the level (100-200 nM) necessary for the optimal operation of the
targets of its regulatory function. The systems that move Ca2+ back and forth across membranes
are important actors in its control. The plasma membrane calcium ATPase (PMCA pump) which ejects
Ca2+ from all eukaryotic cell types will be the topic of this contribution. The pump uses a
molecule of ATP to transport one molecule of Ca2+ from the cytosol to the external environment.
It is a P-type ATPase encoded by four genes (ATP2B1-4), the transcripts of which undergo
different types of alternative splicing. Many pump variants thus exist. Their multiplicity is
best explained by the specific Ca2+ demands in different cell types. In keeping with these
demands, the isoforms are differently expressed in tissues and cell types and have differential
Ca2+ extruding properties. At very low Ca2+ concentrations the PMCAs are nearly inactive. They
must be activated by calmodulin, by acid phospholipids, by protein kinases, and by other means,
e.g., a dimerization process. Other proteins interact with the PMCAs (i.e., MAGUK and NHERF at
the PDZ domain and calcineurin A in the main intracellular domain) to sort them to specific
regions of the cell membrane or to regulate their function. In some cases the interaction is
isoform, or even splice variant specific. PMCAs knock out (KO) mice have been generated and have
contributed information on the importance of PMCAs to cells and organisms. So far, only one human
genetic disease, hearing loss, has been traced back to a PMCA defect. (c) 2008 Elsevier Inc. All
rights reserved. 
PMCA pump; Ca2+ homeostasis; Ca2+ signalling; PMCA KO; hereditary deafness