Cholesterol-Binding Sites in GIRK Channels: The Devil is in the Details

Lipid Insights
Avia Rosenhouse-Dantsker

Abstract

In recent years, it has become evident that cholesterol plays a direct role in the modulation of a variety of ion channels. In most cases, cholesterol downregulates channel activity. In contrast, our earlier studies have demonstrated that atrial G protein inwardly rectifying potassium (GIRK) channels are upregulated by cholesterol. Recently, we have shown that hippocampal GIRK currents are also upregulated by cholesterol. A combined computational-experimental approach pointed to putative cholesterol-binding sites in the transmembrane domain of the GIRK2 channel, the primary subunit in hippocampal GIRK channels. In particular, the principal cholesterol-binding site was located in the center of the transmembrane domain in between the inner and outer α-helices of 2 adjacent subunits. Further studies pointed to a similar cholesterol-binding site in GIRK4, a major subunit in atrial GIRK channels. However, a close look at a sequence alignment of the transmembrane helices of the 2 channels reveals surprising differences among the residues that interact with the cholesterol molecule in these 2 channels. Here, we compare the residues that form putative cholesterol-binding sites in GIRK2 and GIRK4 and discuss the similarities and differe...Continue Reading

References

Sep 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·D Marsh, F J Barrantes
Nov 20, 2009·Channels·Avia Rosenhouse-DantskerIrena Levitan
Sep 11, 2013·The Journal of Biological Chemistry·Avia Rosenhouse-DantskerIrena Levitan
Jul 22, 2015·Biochimica Et Biophysica Acta·Anna N BukiyaAvia Rosenhouse-Dantsker
Feb 19, 2017·The Journal of Biological Chemistry·Anna N BukiyaAvia Rosenhouse-Dantsker
Apr 6, 2017·Biochimica Et Biophysica Acta. Biomembranes·Anna N Bukiya, Avia Rosenhouse-Dantsker
Sep 3, 2017·Current Topics in Membranes·Avia Rosenhouse-Dantsker

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Citations

Apr 5, 2020·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Florina ZakanyZoltan Varga

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