Intracellular Localization of the Glucocorticoid Receptor: Evidence for Cytoplasmic and Nuclear Localization*

Endocrinology ◽  
1987 ◽  
Vol 120 (4) ◽  
pp. 1232-1242 ◽  
Author(s):  
ANN-CHARLOTTE WIKSTRÖM ◽  
ODDMUND BAKKE ◽  
SAM OKRET ◽  
MIKAEL BRÖNNEGÅRD ◽  
JAN-ÅKE GUSTAFSSON
Keyword(s):  
Glucocorticoid Receptor ◽  
Nuclear Localization ◽  
Intracellular Localization

Immunocytochemical study on the intracellular localization of the type 2 glucocorticoid receptor in the rat brain

1987 ◽  
Vol 436 (1) ◽  
pp. 120-128 ◽  
Author(s):  
J.A.M. van Eekelen ◽  
J.Z. Kiss ◽  
H.M. Westphal ◽  
E.R. de Kloet
Keyword(s):  
Glucocorticoid Receptor ◽  
Rat Brain ◽  
Intracellular Localization ◽  
Immunocytochemical Study

scholarly journals Dexamethasone Modulates Nonvisual Opsins, Glucocorticoid Receptor, and Clock Genes inDanio rerioZEM-2S Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Jennifer Caroline Sousa ◽  
Keila Karoline Magalhães-Marques ◽  
Sanseray da Silveira Cruz-Machado ◽  
Maria Nathalia Moraes ◽  
Ana Maria de Lauro Castrucci
Keyword(s):  
Cell Membrane ◽  
Glucocorticoid Receptor ◽  
Nuclear Localization ◽  
Clock Genes ◽  
Clock Synchronization ◽  
Cellular Distribution ◽  
Embryonic Cells ◽  
Light Conditions ◽  
Peripheral Clocks ◽  
First Time

Here we report, for the first time, the differential cellular distribution of two melanopsins (Opn4m1 and Opn4m2) and the effects of GR agonist, dexamethasone, on the expression of these opsins and clock genes, in the photosensitiveD. rerioZEM-2S embryonic cells. Immunopositive labeling for Opn4m1 was detected in the cell membrane whereas Opn4m2 labeling shows nuclear localization, which did not change in response to light.opn4m1,opn4m2,gr,per1b,andcry1bpresented an oscillatory profile of expression in LD condition. In both DD and LD condition, dexamethasone (DEX) treatment shifted the peak expression ofper1bandcry1btranscripts to ZT16, which corresponds to the highestopn4m1expression. Interestingly, DEX promoted an increase ofper1bexpression when applied in LD condition but a decrease when the cells were kept under DD condition. Although DEX effects are divergent with different light conditions, the response resulted in clock synchronization in all cases. Taken together, these data demonstrate thatD. rerioZEM-2S cells possess a photosensitive system due to melanopsin expression which results in an oscillatory profile of clock genes in response to LD cycle. Moreover, we provide evidence that glucocorticoid acts as a circadian regulator ofD. rerioperipheral clocks.

scholarly journals Pendulin, a Drosophila protein with cell cycle-dependent nuclear localization, is required for normal cell proliferation.

1995 ◽  
Vol 129 (6) ◽  
pp. 1491-1507 ◽  
Author(s):  
P Küssel ◽  
M Frasch
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Nuclear Localization ◽  
Growth Regulation ◽  
Tandem Repeats ◽  
Sequence Similarity ◽  
Intracellular Localization ◽  
Abnormal Development ◽  
Embryonic Cells ◽  
Cycle Dependent

We describe the dynamic intracellular localization of Drosophila Pendulin and its role in the control of cell proliferation. Pendulin is a new member of a superfamily of proteins which contains Armadillo (Arm) repeats and displays extensive sequence similarities with the Srp1 protein from yeast, with RAG-1 interacting proteins from humans, and with the importin protein from Xenopus. Almost the entire polypeptide chain of Pendulin is composed of degenerate tandem repeats of approximately 42 amino acids each. A short NH2-terminal domain contains adjacent consensus sequences for nuclear localization and cdc2 kinase phosphorylation. The subcellular distribution of Pendulin is dependent on the phase of cell cycle. During interphase, Pendulin protein is exclusively found in the cytoplasm of embryonic cells. At the transition between G2 and M-phase, Pendulin rapidly translocates into the nuclei where it is distributed throughout the nucleoplasm and the areas around the chromosomes. In the larval CNS, Pendulin is predominantly expressed in the dividing neuroblasts, where it undergoes the same cell cycle-dependent redistribution as in embryos. Pendulin is encoded by the oho31 locus and is expressed both maternally and zygotically. We describe the phenotypes of recessive lethal mutations in the oho31 gene that result in a massive decrease or loss of zygotic Pendulin expression. Hematopoietic cells of mutant larvae overproliferate and form melanotic tumors, suggesting that Pendulin normally acts as a blood cell tumor suppressor. In contrast, growth and proliferation in imaginal tissues are reduced and irregular, resulting in abnormal development of imaginal discs and the CNS of the larvae. This phenotype shows that Pendulin is required for normal growth regulation. Based on the structure of the protein, we propose that Pendulin may serve as an adaptor molecule to form complexes with other proteins. The sequence similarity with importin indicates that Pendulin may play a role in the nuclear import of karyophilic proteins and some of these may be required for the normal transmission and function of proliferative signals in the cells.

scholarly journals REV-ERBα influences stability and nuclear localization of the glucocorticoid receptor

2016 ◽  
pp. jcs.190959 ◽  
Author(s):  
Takashi Okabe ◽  
Rohit Chavan ◽  
Sara S. Fonseca Costa ◽  
Andrea Brenna ◽  
Jürgen A. Ripperger ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Nuclear Localization

scholarly journals Discrimination between NL1- and NL2-Mediated Nuclear Localization of the Glucocorticoid Receptor

1999 ◽  
Vol 19 (2) ◽  
pp. 1025-1037 ◽  
Author(s):  
Joanne G. A. Savory ◽  
Brian Hsu ◽  
Ian R. Laquian ◽  
Ward Giffin ◽  
Terry Reich ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Nuclear Localization ◽  
Nuclear Import ◽  
Nuclear Export ◽  
Binding Domain ◽  
Leptomycin B ◽  
Importin Α ◽  
Agonist And Antagonist ◽  
Import And Export ◽  
Pathway Inhibition

ABSTRACT Glucocorticoid receptor (GR) cycles between a free liganded form that is localized to the nucleus and a heat shock protein (hsp)-immunophilin-complexed, unliganded form that is usually localized to the cytoplasm but that can also be nuclear. In addition, rapid nucleocytoplasmic exchange or shuttling of the receptor underlies its localization. Nuclear import of liganded GR is mediated through a well-characterized sequence, NL1, adjacent to the receptor DNA binding domain and a second, uncharacterized motif, NL2, that overlaps with the ligand binding domain. In this study we report that rapid nuclear import (half-life [t 1/2] of 4 to 6 min) of agonist- and antagonist-treated GR and the localization of unliganded, hsp-associated GRs to the nucleus in G0 are mediated through NL1 and correlate with the binding of GR to pendulin/importin α. By contrast, NL2-mediated nuclear transfer of GR occurred more slowly (t 1/2 = 45 min to 1 h), was agonist specific, and appeared to be independent of binding to importin α. Together, these results suggest that NL2 mediates the nuclear import of GR through an alternative nuclear import pathway. Nuclear export of GR was inhibited by leptomycin B, suggesting that the transfer of GR to the cytoplasm is mediated through the CRM1-dependent pathway. Inhibition of GR nuclear export by leptomycin B enhanced the nuclear localization of both unliganded, wild-type GR and hormone-treated NL1− GR. These results highlight that the subcellular localization of both liganded and unliganded GRs is determined, at least in part, by a flexible equilibrium between the rates of nuclear import and export.

scholarly journals Differential intracellular localization of human mineralocorticosteroid receptor on binding of agonists and antagonists

1994 ◽  
Vol 302 (1) ◽  
pp. 191-197 ◽  
Author(s):  
M Lombès ◽  
N Binart ◽  
F Delahaye ◽  
E E Baulieu ◽  
M E Rafestin-Oblin
Keyword(s):  
Nuclear Localization ◽  
Dna Sequences ◽  
Expression System ◽  
Intracellular Localization ◽  
Baculovirus Expression System ◽  
Target Cells ◽  
Dependent Manner ◽  
Cell Assays ◽  
High Five Cells ◽  
Immunohistochemical Studies

The effect of aldosterone and antimineralocorticoids on the intracellular localization of human mineralocorticosteroid receptor (hMR) was studied using a new monoclonal anti-peptide antibody FD4. This antibody was directed against the peptide hMR-(412-422). As demonstrated by ultracentrifugation analysis, immunoprecipitation assays and Western blot, FD4 recognized both the native and denatured form of the receptor overexpressed in the baculovirus expression system. In whole-cell assays, the amount of hMR recovered in high-salt extracts was significantly lower after exposure to the antimineralocorticoid ZK91587 than to aldosterone, suggesting a lack of nuclear MR translocation. FD4 was also used for immunohistochemical studies on hMR-expressing High Five cells. In the absence of hormone, immunoreactive hMR was detected almost exclusively in the cytoplasmic compartment of cells. After aldosterone exposure, intense nuclear immunostaining appeared in a time-dependent manner, consistent with stable nuclear localization of the receptor. Immunohistochemistry showed that antimineralocorticosteroids (ZK91587, SC9420, 18-vinylprogesterone) predominantly maintained a cytoplasmic distribution of hMR and inhibited its aldosterone-dependent nuclear localization. Thus, in our model, the nuclear/cytoplasmic partition of hMR is drastically different in the presence of antagonists from that in the presence of aldosterone. This phenomenon may contribute to their mechanism of action by preventing productive interaction of antagonist-receptor complex with specific DNA sequences in aldosterone target cells.

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