ATPases PMCA pump

Like the figure of Greek mythology Sisyphus, ATPase pumps are condemned to push Ca + uphill for eternity into the endoplasmic reticulum (ER) (via sarcoendoplasmic reticular Ca + ATPases SERCA pumps) or out of the cell (via plasma membrane Ca " " ATPases PMCA pumps). There is also a family of Ca " " ATPases (pumps), located in the membranes of the Golgi network (the SPCA pumps). All three belong to the family of P-type ATPases,... 

The ER takes up Ca2+ using a sarco(endo)plasmic reticulum ATPase (SERCA) pump (Figure 11.5), which has the same topology with 10 transmembrane domains and the same mechanism of action, with an aspartyl phosphate intermediate, as the PMCA pump described above. 

Abstract The plasma membrane calcium ATPase (PMCA) uses energy to pump calcium (Ca2+)... 

Figure 4. Simplified scheme for the reaction cycle in Ca2+ pumps. The pumps may adopt two major conformations E, and E2. The E, conformation shows high affinity for two Ca2+ (SERCA pumps) or one Ca2+ (PMCA pumps) on the cis side. Ca2+ binding greatly enhances the pumps ATPase activity, leading to the rapid formation of the h igh-energy phosphorylated intermediate E, P and occlusion (occ) of the transported Ca2+ ion(s). Ca2+ translocation across the membrane presumably occurs concomitantly with the release of energy stored as conformational constraint during the transition from the E, P to the low-energy E2-P conformation. Ca2+ affinity on the trans side is low and Ca2+ is therefore released. This is followed by hydrolysis of the phosphoenzyme and a poorly understood rearrangement step(s) from the E2 to the E, conformation.

Ca2+ pumps are divided into two distinct families of plasma membrane and sarco/endoplasmic reticulum membrane Ca2+ ATPases (PMCAs and SERCAs). In tissues with a low Na+/Ca2+ exchanger activity and under conditions unfavorable... 

Calcium pumps, also termed Ca +-ATPase, are calcium channels that transport calcium from the low concentration cytoplasm to the high concentration extracellular space or ER/SR lumenal side using the energy of ATP hydrolysis. Based on their locations, calcium pumps are classified into two groups, plasma membrane Ca +-ATPase (PMCA) and sarcoplasmic reticulum Ca +-ATPase (SERCA). " Four basic isoforms of PMCA (PMCAl 4) have been identified and the other PMCA isoforms are the alternative splicing products of the basic isoforms. PMCAl and 4 are ubiquitously expressed in different tissues and PMCA2 and 3 are expressed in nerve cells. Three basic isoforms of SERCA pump and several sphcing variants have also been identified. ... 

PMCA Plasma membrane Ca + as PMCA-ATPase, a PMCA pump... 

The endoplasmic reticulum takes up Ca " " using the sarco(endo)plasmic reticulum ATPase (SERCA) pump (Figure 11.4). The SERCA pump of many types of muscle is regulated by a protein called phospholambin, which binds to SERCA both in its cytosolic and its transmembrane regions, maintaining the pump in an inactivated state when in its nonphosphorylated form, but detaches from the pump upon phosphorylation, presumably due to a conformational change. In this sense, the SERCA pump is like the PMCA pump, except that Ca -saturated calmodulin activates PMCA, whereas kinase-dependent phosphorylation is involved in SERCA activation (perhaps also dependent on calmodulin). 

Our discussion here will concentrate on the various forms of the Ca " transport ATPases that occur in the sarcoplasmic reticulum of muscle cells of diverse fiber types and in the endoplasmic reticulum of nonmuscle cells (SERCA). The structure of these enzymes will be compared with the Ca transport ATPases of surface membranes (PMCA) [3,29-32,34] and with other ATP-dependent ion pumps that transport Na, K, andH [46,50-52]. 

Figure 1 A schematic representation of the Ca + transporters of animal cells. Plasma membrane (PM) channels are gated by potential, ligands or by the emptying of Ca + stores. Channels in the ER/SR are opened by lnsP3 or cADPr (the cADPr channel is sensitive to ryanodine and is thus called RyR). ATPase pumps are found in the PM (PMCA), in the ER/SR (SERCA), and in the Golgi apparatus (SPCA). The nuclear envelope, which is an extension of ER, contains the same transporters of the latter. NCXs are located in the PM (NCX) and in the inner mitochondria membrane (mNCX). A uniporter (U) driven by the internal negative potential (-180 mV) transports Ca + into mitochondria. Ca +-binding proteins are represented with a sphere containing the four EF-hands Ca +.binding sites.

We discuss now in greater detail the three Ca ATPase pumps (SERCA, PMCA, and SPCA), particularly SERCA for which a vast amount of structural information has been amassed in the course of the last decade. We then present a more detailed description of the intracellular pools of Ca and their exchanges with the cytosol. 

In smooth muscle cells a phosphorylation of the PM Ca2+-pump protein has been clearly demonstrated only for PKC. The regulation of the PMCA ATPase by cGK does not require concomitant phosphorylation of the pump. Although a modulation by cAK of the PM Ca2+ pump of erythrocytes and cardiac cells has been reported, such an effect could not be demonstrated for the ATPase from smooth muscle (see the following). 

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