TY - JOUR
T1 - Glucocorticoid Receptor Localizes to Adherens Junctions at the Plasma Membrane of Keratinocytes
AU - Stojadinovic, Olivera
AU - Sawaya, Andrew
AU - Pastar, Irena
AU - Tomic-Canic, Marjana
PY - 2013/4/30
Y1 - 2013/4/30
N2 - 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.
AB - 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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U2 - 10.1371/journal.pone.0063453
DO - 10.1371/journal.pone.0063453
M3 - Article
C2 - 23646206
AN - SCOPUS:84876986931
VL - 8
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 4
M1 - e63453
ER -