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Region‐specific regulation of glucocorticoid receptor/HSP90 expression and interaction in brain
Author(s) -
Furay A. R.,
Murphy E. K.,
Mattson M. P.,
Guo Z.,
Herman J. P.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03953.x
Subject(s) - glucocorticoid receptor , hsp90 , hippocampal formation , endocrinology , heat shock protein , medicine , hsp70 , biology , glucocorticoid , hypothalamus , receptor , cytosol , intracellular , microbiology and biotechnology , biochemistry , gene , enzyme
The hippocampal glucocorticoid receptor (GR) is involved in negative feedback regulation of the hypothalamo‐pituitary‐adrenal axis and is believed to transduce the deleterious effects of glucocorticoids in depression and age‐related memory loss. Regulation and intracellular trafficking of the GR are critical determinants of GR action in both health and disease. Here, we show dynamic regulation of GR and its interaction with its principal intracellular chaperone, heat‐shock protein (HSP) 90, across the circadian cycle. Our initial experiments indicate that cytosolic hippocampal GR protein is elevated in the evening (PM), whereas nuclear GR and cytosolic HSP90, HSP70 and heat‐shock cognate 70 (HSC70), are unchanged. In contrast, there are no changes in examined proteins in the hypothalamus. Immunoprecipitation experiments reveal increased GR–HSP90 associations in the hippocampus in the PM, whereas binding in the hypothalamus is decreased in the PM. Given that GR requires HSP90 for ligand binding, the data suggest that circadian GR signaling capacity is regulated in a region‐specific pattern.