Glucocorticoid receptor localizes to adherens junctions at the plasma membrane of keratinocytes

PLoS One. 2013 Apr 30;8(4):e63453. doi: 10.1371/journal.pone.0063453. Print 2013.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adherens Junctions / metabolism*
  • Cell Membrane / metabolism
  • Humans
  • Keratinocytes / metabolism*
  • Protein Binding
  • Protein Transport
  • Receptors, Glucocorticoid / metabolism*
  • alpha Catenin / metabolism

Substances

  • Receptors, Glucocorticoid
  • alpha Catenin

Grants and funding

This grant was funded by the sources from the Department of Dermatology of the University of Miami. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.