Phenotypes of SERCA and PMCA knockout mice.
P-type Ca2+-ATPases of the sarco(endo)plasmic reticulum (SERCAs) and plasma membrane (PMCAs) are responsible for maintaining the Ca2+ gradients across cellular membranes that are required for regulation of Ca2+-mediated signaling and other biological processes. Gene-targeting studies of SERCA isoforms 1, 2, and 3 and PMCA isoforms 1, 2, and 4 have confirmed some of the general functions proposed for these pumps, such as a major role in excitation-contraction coupling for SERCA1 and SERCA2 and housekeeping functions for PMCA1 and SERCA2, but have also revealed some unexpected phenotypes. These include squamous cell cancer and plasticity in the regulation of Ca2+-mediated exocytosis in SERCA2 heterozygous mutant mice, modulation of Ca2+ signaling in SERCA3-deficient mice, deafness and balance disorders in PMCA2 null mice, and male infertility in PMCA4 null mice. These unique phenotypes provide new information about the cellular functions of these pumps, the requirement of their activities for higher order physiological processes, and the pathophysiological consequences of pump dysfunction.
Prasad
Vikram
V
Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0524, USA.
Okunade
Gbolahan W
GW
Miller
Marian L
ML
Shull
Gary E
GE
D000818:Animals; D020013:Calcium Signaling; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000473:pathology; D027682:Cation Transport Proteins; D003638:Deafness / Q000209:etiology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D053499:Plasma Membrane Calcium-Transporting ATPases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013081:Sperm Motility
C506944:Atp2a1 protein, mouse; D027682:Cation Transport Proteins; D053499:Plasma Membrane Calcium-Transporting ATPases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506947:Atp2a2 protein, mouse; C506950:Atp2a3 protein, mouse; C506954:Atp2b1 protein, mouse; C506959:Atp2b2 protein, mouse; D000252:Calcium-Transporting ATPases