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Glucocorticoid Receptor Localizes to Adherens Junctions at the Plasma Membrane of Keratinocytes

Glucocorticoids are important regulators of epidermal tissue homeostasis. As such, their clinical applications are widespread, ranging from inflammatory skin disorders to keloids and cancer. Glucocorticoids exert their effect by binding to glucocorticoid receptor (GR) which translocates to the nucle...

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Autores principales: Stojadinovic, Olivera, Sawaya, Andrew, Pastar, Irena, Tomic-Canic, Marjana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639973/
https://www.ncbi.nlm.nih.gov/pubmed/23646206
http://dx.doi.org/10.1371/journal.pone.0063453
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author Stojadinovic, Olivera
Sawaya, Andrew
Pastar, Irena
Tomic-Canic, Marjana
author_facet Stojadinovic, Olivera
Sawaya, Andrew
Pastar, Irena
Tomic-Canic, Marjana
author_sort Stojadinovic, Olivera
collection PubMed
description Glucocorticoids are important regulators of epidermal tissue homeostasis. As such, their clinical applications are widespread, ranging from inflammatory skin disorders to keloids and cancer. Glucocorticoids exert their effect by binding to glucocorticoid receptor (GR) which translocates to the nucleus and regulates gene expression (genomic effect). In addition, GR has rapid non- genomic effects that are mediated by cell signaling proteins and do not involve gene transcription. Although genomic effects of GR in the epidermis are well documented, the non-genomic effects are not completely understood. Therefore, we utilized immunostaining and immunoprecipitations to determine specific localization of the GR in human keratinocytes that may contribute to non-genomic effects of glucocorticoid action. Here we describe a novel finding of GR localization to the plasma membrane of keratinocytes. Immunocytochemistry showed co-localization of GR with α-catenin. Immunoprecipitation of the membranous fraction revealed an association of GR with α-catenin, confirming its localization to adherens junctions. We conclude that GR localization to adherens junctions of keratinocytes provides a new mechanism of non-genomic signaling by glucocorticoids which may have significant biological and clinical impact.
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spelling pubmed-36399732013-05-03 Glucocorticoid Receptor Localizes to Adherens Junctions at the Plasma Membrane of Keratinocytes Stojadinovic, Olivera Sawaya, Andrew Pastar, Irena Tomic-Canic, Marjana PLoS One Research Article Glucocorticoids are important regulators of epidermal tissue homeostasis. As such, their clinical applications are widespread, ranging from inflammatory skin disorders to keloids and cancer. Glucocorticoids exert their effect by binding to glucocorticoid receptor (GR) which translocates to the nucleus and regulates gene expression (genomic effect). In addition, GR has rapid non- genomic effects that are mediated by cell signaling proteins and do not involve gene transcription. Although genomic effects of GR in the epidermis are well documented, the non-genomic effects are not completely understood. Therefore, we utilized immunostaining and immunoprecipitations to determine specific localization of the GR in human keratinocytes that may contribute to non-genomic effects of glucocorticoid action. Here we describe a novel finding of GR localization to the plasma membrane of keratinocytes. Immunocytochemistry showed co-localization of GR with α-catenin. Immunoprecipitation of the membranous fraction revealed an association of GR with α-catenin, confirming its localization to adherens junctions. We conclude that GR localization to adherens junctions of keratinocytes provides a new mechanism of non-genomic signaling by glucocorticoids which may have significant biological and clinical impact. Public Library of Science 2013-04-30 /pmc/articles/PMC3639973/ /pubmed/23646206 http://dx.doi.org/10.1371/journal.pone.0063453 Text en © 2013 Stojadinovic et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Stojadinovic, Olivera
Sawaya, Andrew
Pastar, Irena
Tomic-Canic, Marjana
Glucocorticoid Receptor Localizes to Adherens Junctions at the Plasma Membrane of Keratinocytes
title Glucocorticoid Receptor Localizes to Adherens Junctions at the Plasma Membrane of Keratinocytes
title_full Glucocorticoid Receptor Localizes to Adherens Junctions at the Plasma Membrane of Keratinocytes
title_fullStr Glucocorticoid Receptor Localizes to Adherens Junctions at the Plasma Membrane of Keratinocytes
title_full_unstemmed Glucocorticoid Receptor Localizes to Adherens Junctions at the Plasma Membrane of Keratinocytes
title_short Glucocorticoid Receptor Localizes to Adherens Junctions at the Plasma Membrane of Keratinocytes
title_sort glucocorticoid receptor localizes to adherens junctions at the plasma membrane of keratinocytes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639973/
https://www.ncbi.nlm.nih.gov/pubmed/23646206
http://dx.doi.org/10.1371/journal.pone.0063453
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