Glucocorticoid receptor isoforms direct distinct mitochondrial programs to regulate ATP production

The glucocorticoid receptor (GR), a nuclear receptor and major drug target, has a highly conserved minor splice variant, GRγ, which differs by a single arginine within the DNA binding domain. GRγ, which comprises 10% of all GR transcripts, is constitutively expressed and tightly conserved through ma...

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Main Authors:	Morgan, David J., Poolman, Toryn M., Williamson, Andrew J. K., Wang, Zichen, Clark, Neil R., Ma’ayan, Avi, Whetton, Anthony D., Brass, Andrew, Matthews, Laura C., Ray, David W.
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881047/

id	pubmed-4881047
recordtype	oai_dc
spelling	pubmed-48810472016-06-08 Glucocorticoid receptor isoforms direct distinct mitochondrial programs to regulate ATP production Morgan, David J. Poolman, Toryn M. Williamson, Andrew J. K. Wang, Zichen Clark, Neil R. Ma’ayan, Avi Whetton, Anthony D. Brass, Andrew Matthews, Laura C. Ray, David W. Article The glucocorticoid receptor (GR), a nuclear receptor and major drug target, has a highly conserved minor splice variant, GRγ, which differs by a single arginine within the DNA binding domain. GRγ, which comprises 10% of all GR transcripts, is constitutively expressed and tightly conserved through mammalian evolution, suggesting an important non-redundant role. However, to date no specific role for GRγ has been reported. We discovered significant differences in subcellular localisation, and nuclear-cytoplasmic shuttling in response to ligand. In addition the GRγ transcriptome and protein interactome was distinct, and with a gene ontology signal for mitochondrial regulation which was confirmed using Seahorse technology. We propose that evolutionary conservation of the single additional arginine in GRγ is driven by a distinct, non-redundant functional profile, including regulation of mitochondrial function. Nature Publishing Group 2016-05-26 /pmc/articles/PMC4881047/ /pubmed/27226058 http://dx.doi.org/10.1038/srep26419 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Morgan, David J. Poolman, Toryn M. Williamson, Andrew J. K. Wang, Zichen Clark, Neil R. Ma’ayan, Avi Whetton, Anthony D. Brass, Andrew Matthews, Laura C. Ray, David W.
spellingShingle	Morgan, David J. Poolman, Toryn M. Williamson, Andrew J. K. Wang, Zichen Clark, Neil R. Ma’ayan, Avi Whetton, Anthony D. Brass, Andrew Matthews, Laura C. Ray, David W. Glucocorticoid receptor isoforms direct distinct mitochondrial programs to regulate ATP production
author_facet	Morgan, David J. Poolman, Toryn M. Williamson, Andrew J. K. Wang, Zichen Clark, Neil R. Ma’ayan, Avi Whetton, Anthony D. Brass, Andrew Matthews, Laura C. Ray, David W.
author_sort	Morgan, David J.
title	Glucocorticoid receptor isoforms direct distinct mitochondrial programs to regulate ATP production
title_short	Glucocorticoid receptor isoforms direct distinct mitochondrial programs to regulate ATP production
title_full	Glucocorticoid receptor isoforms direct distinct mitochondrial programs to regulate ATP production
title_fullStr	Glucocorticoid receptor isoforms direct distinct mitochondrial programs to regulate ATP production
title_full_unstemmed	Glucocorticoid receptor isoforms direct distinct mitochondrial programs to regulate ATP production
title_sort	glucocorticoid receptor isoforms direct distinct mitochondrial programs to regulate atp production
description	The glucocorticoid receptor (GR), a nuclear receptor and major drug target, has a highly conserved minor splice variant, GRγ, which differs by a single arginine within the DNA binding domain. GRγ, which comprises 10% of all GR transcripts, is constitutively expressed and tightly conserved through mammalian evolution, suggesting an important non-redundant role. However, to date no specific role for GRγ has been reported. We discovered significant differences in subcellular localisation, and nuclear-cytoplasmic shuttling in response to ligand. In addition the GRγ transcriptome and protein interactome was distinct, and with a gene ontology signal for mitochondrial regulation which was confirmed using Seahorse technology. We propose that evolutionary conservation of the single additional arginine in GRγ is driven by a distinct, non-redundant functional profile, including regulation of mitochondrial function.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881047/
_version_	1613584458465673216

Glucocorticoid receptor isoforms direct distinct mitochondrial programs to regulate ATP production

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