The Plasma Membrane Ca2+ ATPase

Abstract

The plasma membrane Ca2+ ATPase (PMCA) or Ca2+ pump transports Ca2+ ions out of the cells by using the energy stored in ATP. The plasma membrane Ca2+ pump has been found not only in all mammalian cells, but also in varieties of invertebrates and in yeast. So far no PMCA genes have been found in bacteria. The biochemical and biophysical properties of the pump have been primarily studied on the enzyme purified from the membrane of the red blood cells but, recently, molecular biological methods have been successfully used to study the properties of the different PMCA isoforms. The plasma membrane pump is encoded by four genes and alternative splicing at two independent sites increases the number of the possible isoforms: transcripts for more than 20 isoforms have been detected. Some of the PMCA variants have a different affinity to calmodulin. The activity of these alternatively spliced pumps is possibly differently regulated by kinase-mediated phosphorylation. Here an update will be presented on the regulation of the expression of PMCA genes and splice variants, on the subcellular distribution of the protein and on the mechanism by which the PMCA pump translocates Ca2+ through the plasma membrane. Genetic evidence indicates that PMCA2, one of the isoforms expressed at high level only in brain, is responsible for hearing defects in mice.