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Gene knockout studies of Ca$^2+$-transporting ATPases.

. Eur. J. Biochem. 267 (17): 5284--5290 (September 2000)

Abstract

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.

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