SERCA ATPase

Protein kinase A (PKA) is a cyclic AMP-dependent protein kinase, a member of a family of protein kinases that are activated by binding of cAMP to their two regulatory subunits, which results in the release of two active catalytic subunits. Targets of PKA include L-type calcium channels (the relevant subunit and site of phosphorylation is still uncertain), phospholam-ban (the regulator of the sarcoplasmic calcium ATPase, SERCA) and key enzymes of glucose and lipid metabolism. 

Sarcoplasmic reticulum (SR) is a form of the smoothfaced endoplasmic reticulum (ER) in muscles. It functions as an intracellular Ca2+ store for muscle contraction. Ca2+ is energetically sequestered into the SR by Ca2+-pump/sarcoplasmic endoplasmic reticulum Ca2+-ATPase (SERCA) and released via Ca2+ release channels on stimuli (ryanodine receptor in striated muscles and inositol 1,4,5-trisphosphate receptor in most smooth muscles). Endoplasmic reticulum in non-muscle tissues also functions as an intracellular Ca2+ store. 

Phospholamban (PLB or PLN) is a single-pass, 52-residue integral membrane protein that regulates myocardial contractility by direct physical interaction with sarco(endo)plasmic reticulum Ca-ATPase (SERCA), a 110-kDa enzyme that maintains calcium homeostasis in the sarcoplasmic... 

The only known mechanism for Ca2+ accumulation by the endoplasmic reticulum is by means of sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) pumps 381... 

The plasma membrane Ca2+-ATPase pump effects outward transport of Ca2+ against a large electrochemical gradient for Ca2+. The mechanism of the pump involves its phosphorylation by ATP and the formation of a high-energy intermediate. This basic mechanism is similar for both the plasma membrane and ER pumps however, the structures of these distinct gene products are substantially different. As discussed below, the ER pump, sometimes called a sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) pump, is inhibited potently by certain natural and synthetic toxins that do not affect the plasma membrane pump. The plasma membrane pump, but not the SERCA pump, is controlled in part by Ca2+ calmodulin, allowing for rapid activation when cytoplasmic Ca2+ rises. 

FIGURE 22-3 Structures of compounds that inhibit sarcoendoplas-mic reticulum Ca2+-ATPase (SERCA) calcium pumps. 

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. 

Some sarco(endo)plasmic reticulum (SR) Ca +-ATPases (SERCA) are P-type ATPases that play a major role in muscle contraction-relaxation cycles and are responsible for transporting calcium into the lumen of the sarcoplasmic reticulum. Some definitions are useful in the discussion of Ca +-ATPases ... 

Cyclopiazonic acid is a potent inhibitor of calcium uptake and acts as a selective inhibitor of the sarco-endoplasmic reticulum Ca2+ATPases (SERCAs) [53], it induces charge alteration in plasma membranes and mitochondria and it can function as an antioxidant [54]. 

Adds new details to the discussion of the mechanism of Ca2- ATPase (SERCA... 

Keywords Sarco(endo)plasmic reticulum (SER) Ca2+-ATPases (SERCA), ATP2A1, ATP2A2,... 

Asahi, M., Sugita, Y., Kurzydlowski, K., De Leon, S., Tada, M., Toyoshima, C., and MacLennan, D. H., 2003, Sarcolipin regulates sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) by binding to transmembrane helices alone or in association with phospholamban. Proc Natl Acad Sci USA, 100 5040-5. 

Dode, L., Andersen, J. P., Leshe, N., Dhitavat, J., Vilsen, B., and Hovnanian, A., 2003, Dissection of the functional differences between sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) 1 and 2 isoforms and characterization of Darier disease (SERCA2) mutants by steady-state and transient kinetic analyses. J Biol Chem, 278 47877—89. 

Martin, V., Bredoux, R., Corvazier, E., Van Gorp, R., Kovacs, T., Gelebart, P., and Enouf, J., 2002, Three novel sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) 3 isoforms. Expression, regulation, and function of the membranes of the SERCA3 family. J Biol Chem, 277 24442-52. 

Table 5. Characteristics of Sarco(endo)plasmic Reticulum Ca2+-ATPase (SERCA) Isoforms and Tissue Distribution of Isoform mRNAs...

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. ... 

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