Regulation of Cell Calcium and Role of Plasma Membrane Calcium ATPases

The plasma membrane Ca²⁺ ATPase (PMCA pump) is a member of the superfamily of P-type pumps. It has 10 transmembrane helices and 2 cytosolic loops, one of which contains the catalytic center. Its most distinctive feature is a C-terminal tail that contains most of the regulatory sites including that for calmodulin. The pump is also regulated by acidic phospholipids, kinases, a dimerization process, and numerous protein interactors. In mammals, four genes code for the four basic isoforms. Isoform complexity is increased by alternative splicing of primary transcripts. Pumps 2 and 3 are expressed preferentially in the nervous system. The pumps coexist with more powerful systems that clear Ca²⁺ from the bulk cytosol: their role is thus the regulation of Ca²⁺ in selected subplasma membrane microdomains, where a number of important Ca²⁺-dependent enzymes interact with them. Malfunctions of the pump lead to disease phenotypes that affect the nervous system preferentially.