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Signaling by Calcium and the RHOA GTPASE: Relating Structure to Function

Published online by Cambridge University Press:  02 July 2020

A.P. Somlyo
Affiliation:
Dept. of Molecular Physiology and Biological Physics, Univ. of Virginia, Charlottesville, VA22908
A.V. Somlyo
Affiliation:
Dept. of Molecular Physiology and Biological Physics, Univ. of Virginia, Charlottesville, VA22908
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Extract

We will review the results of structural approaches used in our laboratory for evaluating the roles of calcium (Ca2+) and the small GTPase, RhoA, in normal and pathological cell signaling.

An early method, using strontium (Sr) as an electron opaque marker of mitochondrial Ca, was first used to localize this “Ca2+ surrogate” in the sarcoplasmic reticulum (SR) of smooth muscle. Subsequent development of electron probe X-ray microanalysis (EPMA) and electron energy-loss spectroscopy (EELS) allowed the direct and quantitative detection of intracellular Ca in smooth, skeletal and cardiac muscles. The major conclusion of these studies was that, in all muscles, the SR is the major intracellular sink/source of activator Ca2+. The high ratio of total/free cytoplasmic Ca2+ indicated the presence of significant cytoplasmic Ca buffers not only in striated, but also in smooth muscles, and EPMA of frog skeletal muscle showed that the time course of changes in cytoplasmic Ca during relaxation was consistent with the off-rate of Ca2+ from the Ca2+-buffer, parvalbumin.

Type
Philadelphia—The Other Motor City: Muscle and Non-Muscle Motility. A Dedication to Dr. Lee Peachey
Copyright
Copyright © Microscopy Society of America

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