Gene knockout studies of Ca2+-transporting ATPases

The biochemical functions of intracellular and plasma membrane Ca2+-transpo rting ATPases in the control of cytosolic and organellar Ca2+ levels are we ll established, but the physiological roles of specific isoforms are less w ell understood. There appear to be three different types of Ca2+ pumps in m ammalian tissues: the sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs), w hich sequester Ca2+ within the endoplasmic or sarcoplasmic reticulum, the p lasma membrane Ca2+-ATPases (PMCAs), which extrude Ca2+ from the cell, and the putative secretory pathway Ca2+-ATPase (SPCA), the function of which is poorly understood. This review describes the results of recent analyses of mouse models with null mutations in the genes encoding SERCA and PMCA isof orms and genetic studies of SERCA and SPCA dysfunction in both humans and m odel organisms. These studies are yielding important insights regarding the physiological functions of individual Ca2+-transporting ATPases in vivo.