The Plasma Membrane Calcium Pump: New Ways to Look at an Old Enzyme

The three-dimensional structure of the PMCA pump has not been solved, but its basic mechanistic properties are known to repeat those of the other Ca2+ pumps. However, the pump also has unique properties. They concern essentially its numerous regulatory mechanisms, the most important of which is the autoinhibition by its C-terminal tail. Other regulatory mechanisms involve protein kinases and the phospholipids of the membrane in which the pump is embedded. Permanent activation of the pump, e.g. by calmodulin, is physiologically as harmful to cells as its absence. The concept is now emerging that the global control of cell Ca2+ may not be the main function of the pump; in some cell types, it could even be irrelevant. The main pump role would be the regulation of Ca2+ in cell microdomains in which the pump co-segregates with partners that modulate the Ca2+ message and transduce it to important cell functions.