title: Plasma membrane calcium ATPases: From generic Ca(2+) sump pumps to versatile systems for fine-tuning cellular Ca(2.).
abstract: The plasma membrane calcium ATPases (PMCAs) are ATP-driven primary ion pumps found in all eukaryotic cells. They are the major high-affinity calcium extrusion system for expulsion of Ca(2+) ions from the cytosol and help restore the low resting levels of intracellular [Ca(2+)] following the temporary elevation of Ca(2+) generated during Ca(2+) signaling. Due to their essential role in the maintenance of cellular Ca(2+) homeostasis they were initially thought to be "sump pumps" for Ca(2+) removal needed by all cells to avoid eventual calcium overload. The discovery of multiple PMCA isoforms and alternatively spliced variants cast doubt on this simplistic assumption, and revealed instead that PMCAs are integral components of highly regulated multi-protein complexes fulfilling specific roles in calcium-dependent signaling originating at the plasma membrane. Biochemical, genetic, and physiological studies in gene-manipulated and mutant animals demonstrate the important role played by specific PMCAs in distinct diseases including those affecting the peripheral and central nervous system, cardiovascular disease, and osteoporosis. Human PMCA gene mutations and allelic variants associated with specific disorders continue to be discovered and underline the crucial role of different PMCAs in particular cells, tissues and organs.
authors.affiliation: Department of Biochemistry and Molecular Biology, Guggenheim 16-11A1, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. Electronic address: strehler.emanuel@mayo.edu.
authors.forename: Emanuel E
authors.initials: EE
authors.lastname: Strehler
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D008954:Models, Biological
chemical_list: D000252:Calcium-Transporting ATPases; D002118:Calcium
keywords: ATP2B ion pumps; Calcium microdomain; Calcium signaling; PMCA disease; Plasma membrane calcium ATPase