SERCA pump isoforms: Their role in calcium transport and disease

Abstract

The sarcoendoplasmic reticulum (SR) calcium transport ATPase (SERCA) is a pump that transports calcium ions from the cytoplasm into the SR. It is present in both animal and plant cells, although knowledge of SERCA in the latter is scant. The pump shares the catalytic properties of ion-motive ATPases of the P-type family, but has distinctive regulation properties. The SERCA pump is encoded by a family of three genes, SERCA1, 2, and 3, that are highly conserved but localized on different chromosomes. The SERCA isoform diversity is dramatically enhanced by alternative splicing of the transcripts, occurring mainly at the COOH-terminal. At present, more than 10 different SERCA isoforms have been detected at the protein level. These isoforms exhibit both tissue and developmental specificity, suggesting that they contribute to unique physiological properties of the tissue in which they are expressed. The function of the SERCA pump is modulated by the endogenous molecules phospholamban (PLB) and sarcolipin (SLN), expressed in cardiac and skeletal muscles. The mechanism of action of PLB on SERCA is well characterized, whereas that of SLN is only beginning to be understood. Because the SERCA pump plays a major role in muscle contraction, a number of investigations have focused on understanding its role in cardiac and skeletal muscle disease. These studies document that SERCA pump expression and activity are decreased in aging and in a variety of pathophysiological conditions including heart failure. Recently, SERCA pump gene transfer was shown to be effective in restoring contractile function in failing heart muscle, thus emphasizing its importance in muscle physiology and its potential use as a therapeutic agent.

The non-excitable smooth muscle: Calcium signaling and phenotypic switching during vascular disease

“…The SERCA pump is encoded by a family of three genes located on separate chromosomes, SERCA1, 2, and 3 [44]. The SERCA isoform diversity is greatly increased by alternative splicing of the transcripts, resulting in more than ten different SERCA isoforms currently characterized in different tissues and developmental states [106]. SERCA isoforms differ in their affinity for Ca 2+ , resistance to oxidative stress and modulation by phospholamban (PLN) and Ca 2+ /calmodulin kinase II.…”

The mechanisms of calcium homeostasis and signalling in the lens

“…Its action, in combination with Ca 2þ efflux mechanisms, is essential in maintaining a low resting [Ca 2þ ] i . There are 3 isoforms (SERCA1-3) coded for by three genes and multiple splice variants, producing more than 10 different isoforms, have been described (Periasamy and Kalyanasundaram, 2007). The human lens expresses isoforms SERCA2b and SERCA3 (Liu et al, 1999).…”

“…The human lens expresses isoforms SERCA2b and SERCA3 (Liu et al, 1999). Functional differences between the isoforms, such as affinity for Ca 2þ and pump velocity have been identified (Periasamy and Kalyanasundaram, 2007) and tissue-specific expression profiles presumably reflect the specific Ca 2þ dynamics of particular cell types.…”

El acoplamiento excitación-contracción en el músculo esquelético: preguntas por responder a pesar de 50 años de estudio

“…La SERCA es una proteína de 110 kDa ubicada básicamente en la región longitudinal del retículo sarcoplásmico; la regulación de su expresión y función es bastante compleja, e incluye el Ca 2+ , el pH, las hormonas tiroideas y las proteínas fosfolambán y sarcolipina (7,(39)(40)(41)(42)(43)(44). La proteína tiene tres grandes dominios citoplásmicos unidos a un dominio que consta de 10 hélices hidrofóbicas que atraviesan la membrana del retículo sarcoplásmico.…”