THE PLASMA-MEMBRANE CALCIUM-PUMP - RECENT DEVELOPMENTS AND FUTURE PERSPECTIVES

The Ca2+ pump of the plasma membrane (PMCA) is regulated by a number o f agents. The most important is calmodulin (CaM), which binds to a dom ain located in the C-terminal portion of the pump, removing it from an autoinhibitory site next to the active site. The CaM-binding domain i s preceded by an acidic sequence which contains a hidden signal for en doplasmic reticulum (ER) retention. Chimeras of the PMCA and endoplasm ic reticulum (SERCA) pumps have revealed the presence of a strong sign al for ER retention in the first 45 residues of the SERCA pump. Four g ene products of the PMCA pump are known: two of them (1 and 4) are ubi quitously expressed, two (2 and 3) are specific for nerve cells and ma y be induced by their activation. Mutagenesis work has identified four residues in three of the transmembrane domains of the pump which may be components of the trans-protein Ca2+ path. The mutation of two of t hese residues alters the membrane targeting of the pump.