Gene knockout studies of Ca$^2+$-transporting ATPases.
G. Shull. Eur. J. Biochem.267 (17):
The biochemical functions of intracellular and plasma membrane Ca$^2+$-transporting
ATPases in the control of cytosolic and organellar Ca$^2+$ levels
are well established, but the physiological roles of specific isoforms
are less well understood. There appear to be three different types
of Ca$^2+$ pumps in mammalian tissues: the sarco(endo)plasmic
reticulum Ca$^2+$-ATPases (SERCAs), which sequester Ca$^2+$
within the endoplasmic or sarcoplasmic reticulum, the plasma membrane
Ca$^2+$-ATPases (PMCAs), which extrude Ca$^2+$ from the
cell, and the putative secretory pathway Ca$^2+$-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 isoforms and genetic studies
of SERCA and SPCA dysfunction in both humans and model organisms.
These studies are yielding important insights regarding the physiological
functions of individual Ca$^2+$-transporting ATPases in vivo.