Pump Isoforms

Isoforms of the Endoplasmic Reticulum-T)q e Ca + Pumps (SERCA Pumps) 

SERCA2b is probably ubiquitously expressed and can be considered as a housekeeping isoform. Alternative splicing of SERCA2 to the 2a isoform only occurs in cardiac muscle, slow skeletal muscle, and to some extent also in smooth muscle (Gunteski-Hamblin et al., 1988 Eggermont et al., 1990b). The nu- 

It is beyond the scope of this chapter to overview the complex isoform diversity generated by alternative splicing of the primary transcripts of the four recognized PMCA genes. The isoform diversity has been updated and reviewed by Carafoli (1994). The following is intended to represent the most essential information. 

Because of the limited availability of pure protein preparations of specific isoforms, little is known of the functional properties of the different isoforms and their regulation. 

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The reactivity of the sodium pump isoforms toward ouabain can significantly differ between certain isoenzymes. The al-isoform from rat is reported to be 100-fold more resistant to ouabain than a2- or a3-isoform. In other species like rabbit, pig, dog or human these differences are not as distinct as in rat, due to a more sensitive al-isoform. At least two different types of ouabain binding sites are reported for the Na+/fC+-ATPase [1]. 

Genetic evidence supports the importance of coordinated expression and distributions of a2 or a3 Na+/K+ pump isoforms with the Na+/Ca2+ exchanger (NCX) and Ca2+ pumps to function in excitable and contractile cells deletion of one copy of the a2 Na+/K+ pump gene in mice leads to increased contractile force in cardiac and skeletal muscle while deletion of one copy of the al gene leads to reduction of contractile force [25]. In rat optic nerve astrocytes, deletion of the a2 gene or ouabain treatment of cells expressing a2 leads to increased capacitative calcium entrance responses, which reflect a decreased ability to rapidly remove cytosolic Ca2+ [26]. 

Eggermont JA, Wuytack F, Verbist J, Casteels R 1990 Expression of endoplasmic-reticulum Ca2+-pump isoforms and of phospholamban in pig smooth-muscle tissues. Biochem J... 

Periasamy, M., and Kalyanasundaram, A., 2007, SERCA pump isoforms Their role in calcium transport and disease. Muscle Nerve. 

Brini, M., Coletto, L., Pierobon, N., Kraev, N., Guerini, D., Carafoli, E., 2003, A comparative functional analysis of plasma membrane Ca2+ pump isoforms in intact cells. J Biol Chem 278, 24500-24508. 

Hilfiker, H., Strehler-Page, M.A., Stauffer, T.P., Carafoli, E., Strehler, E.E., 1993, Structure of the gene encoding the human plasma membrane calcium pump isoform 1. J Biol Chem 268, 19717-19725. 

Lee, W.J., Roberts-Thomson, S.J., Holman, N.A., May, F.J., Lehrbach, G.M., Monteith, G.R., 2002, Expression of plasma membrane calcium pump isoform mRNAs in breast cancer cell lines. Cell Signal 14, 1015-1022. 

Papp, B Enyedi, A., Paszty, K., Kov4cs, T., Sarkadi, B., G dos, G., Magnier, C Wuytack, F., Enouf, J. (1992). Simultaneous presence of two distinct endoplasmic-reticulum-type calcium-pump isoforms in human cells. Biochem. J. 288,297-302. 

Guerini D, Garcia-Martin E, Gerber A, Volbracht C, Leist M, Merino CG, Carafoli E. The expression of plasma membrane Ca + pump isoforms in cerebellar granule neurons is modulated by Ca +. J. Biol. Chem. 1999 274 1667-1676. 

In cardiac muscle, the increased activity of the Ca + pump of the SR as a consequence of the phosphorylation of phospholamban plays a key role in the positive chronotropic and inotropic action of -receptor agonists (Tada and Kadoma, 1989 Luo et al., 1994). The highest levels of expression of phospholamban are found in cardiac and in slow skeletal muscle, the two muscle types that express SERCA2a as the major Ca2+-pump isoform. East skeletal muscle, which expresses SERCAl, does not contain phospholamban. Coexpression studies have shown, however, that phospholamban is able to interact with the SERCAl pump (Fujii et al, 1990). 

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