Multifaceted plasma membrane Ca2+ pumps: From structure to intracellular Ca2+ handling and cancer

Plasma membrane Ca2+ ATPases (PMCAs) are intimately involved in the control of intracellular Ca2+ concentration. They reduce Ca2+ in the cytosol not only by direct ejection, but also by controlling the formation of inositol-1,4,5-trisphosphate and decreasing Ca2+ release from the endoplasmic reticulum Ca2+ pool. In mammals four genes (PMCA1-4) are expressed, and alternative RNA splicing generates more than twenty variants. The variants differ in their regulatory characteristics. They localize into highly specialized membrane compartments and respond to the incoming Ca2+ with distinct temporal resolution. The expression pattern of variants depends on cell type; a change in this pattern can result in perturbed Ca2+ homeostasis and thus altered cell function. Indeed, PMCAs undergo remarkable changes in their expression pattern during tumorigenesis that might significantly contribute to the unbalanced Ca2+ homeostasis of cancer cells