The plasma membrane calcium pump

Abstract

The plasma membrane Ca 2+ -ATPase (PMCA) is the high Ca 2+ -affinity system that maintains the intracellular free Ca 2+ at the appropriately low level in all eukaryotic cells. It is a member of the P-type ATPases family, which is regulated by a number of factors/processes, chiefly, by the interaction with calmodulin. In mammals, it is the product of four independent genes: two of the gene products are ubiquitous (PMCA1 and 4) and two are tissue-restricted (essentially neuronal). A number of alternative splicing processes increase the multiplicity of isoforms. The rationale for the existence of so many PMCA pump variants is not understood but may reflect the interaction with isoform-specific regulatory protein partners. Several such partners have been identified, and recent work has shown that one of them (protein 14.3.3ε) only interacts with some of the pump isoforms. Genetic defects of the PMCAs are beginning to be identified. The most interesting affects PMCA2, which is abundantly expressed in the outer hair cells of the inner ear. A number of mutations in the PMCA2 pump gene have been shown to produce hereditary hearing loss in mice and in humans.