Plasma Membrane Calcium Pump: Structure and Function

Plasma membrane Ca2þ-adenosine triphosphatases (ATPases) (PMCAs) are high-affinity calcium pumps that contribute to the maintenance of intracellular Ca2þ homeostasis by exporting Ca2þ from the cytosol to the extracellular environment. Mammals have four genes, encoding the proteins PMCA1 through PMCA4. Each gene transcript is alternatively spliced to generate several variants. Their distribution is tissue and cell specific and undergoes regulation during cell development and differentiation. Traditionally, these pumps have been considered to play a housekeeping role in controlling basal Ca2þ levels but more recently it became clear that the presence (and the co-expression) of different isoforms must be related to a more specialized function. Only one of the four genes (that encodes PMCA2) has been causally linked to disease in mammals: several spontaneous mutations are responsible for hereditary deafness and ataxia. Other complex human disease phenotypes such as cancer, cardiac dysfunction, and infertility are likely to be associated with PMCA function but no direct link with its mutations has been reported so far.