Molecular physiology of the SERCA and SPCA pumps

Intracellular Ca2+-transport ATPases exert a pivotal role in the endoplasmic reticulum and in the compartments of the cellular secretory pathway by maintaining a sufficiently high lumenal Ca2+ (and Mn2+) concentration in these compartments required for an impressive number of vastly different cell functions. At the same time this lumenal Ca2+ represents a store of releasable activator Ca2+ controlling an equally impressive number of cytosolic functions. This review mainly focuses on the different Ca2+-transport ATPases found in the intracellular compartments of mainly animal non-muscle cells: the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) pumps. Although it is not our intention to treat the ATPases of the specialized sarcoplasmic reticulum in depth, we can hardly ignore the SERCA1 pump of fast-twitch skeletal muscle since its structure and function is by far the best understood and it can serve as a guide to understand the other members of the family. In a second part of this review we describe the relatively novel family of secretory pathway Ca2+/Mn2+ ATPases (SPCA), which in eukaryotic cells are primarily found in the Golgi compartment.