Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor
In the absence of hormone, corticosteroid receptors are primarily located in the cytoplasm, and they rapidly accumulate in the nucleus (t0.5 = 5 min) upon ligand binding. It is generally believed that the dissociation of hsp90 from the receptor is an absolute requirement for allowing its nuclear tra...
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todo:paper_00062960_v46_n5_p1389_Pilipuk2023-10-03T14:04:27Z Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor Pilipuk, G.P. Vinson, G.P. Sanchez, C.G. Galigniana, M.D. Antibodies Biological organs Cells Chemical bonds Dissociation Hormones Proteins Glucocorticoid receptors Mineralocorticoid receptor (MR) Nuclear accumulation Nuclear localization signals (NLS) Neurology aldosterone corticosteroid receptor digitonin heat shock protein 90 mineralocorticoid receptor animal cell article carbamoylation cell membrane permeability cell nucleus controlled study cytoplasm dissociation kidney collecting tubule ligand binding mouse nonhuman nuclear localization signal priority journal protein localization rat Active Transport, Cell Nucleus Aldosterone Animals HSP90 Heat-Shock Proteins Kidney Kinetics Nuclear Localization Signals Rats Receptors, Mineralocorticoid Rattus In the absence of hormone, corticosteroid receptors are primarily located in the cytoplasm, and they rapidly accumulate in the nucleus (t0.5 = 5 min) upon ligand binding. It is generally believed that the dissociation of hsp90 from the receptor is an absolute requirement for allowing its nuclear translocation. However, recent evidence suggests that hsp90 may remain associated with the glucocorticoid receptor during this process, and thus, the receptor nuclear localization signal (NLS) is not obscured by its presence. To determine the requirements for mineralocorticoid receptor (MR) nuclear transport, it was first shown that in rat kidney collecting duct cells, nuclear localization of MR in the presence of aldosterone was complete in 10 min. Although the hsp90 inhibitor radicicol delayed nuclear translocation, it did not prevent complete nuclear accumulation of MR at longer incubation times (t 0.5 = 30-40 min). MR carbamylation generates a non-steroid- transformed receptor that, in contrast to native MR, is very stable in cell-free systems. In contrast to the full nuclear translocation of aldosterone- transformed MR, only a fraction of the carbamylated MR became nuclear in digitonin-permeabilized cells even though its NLS is exposed. Furthermore, while preincubation of permeabilized cells with NL1 peptide or anti-NL1 antibody fully inhibited the nuclear translocation of NL1-tagged albumin, neither treatment fully inhibited MR nuclear translocation. We postulate that there are at least two possible mechanisms for MR nuclear translocation. One of them is hsp90- and NL1-dependent, and the other functions in a manner that is independent of the classical pathway. © 2007 American Chemical Society. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00062960_v46_n5_p1389_Pilipuk |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Antibodies Biological organs Cells Chemical bonds Dissociation Hormones Proteins Glucocorticoid receptors Mineralocorticoid receptor (MR) Nuclear accumulation Nuclear localization signals (NLS) Neurology aldosterone corticosteroid receptor digitonin heat shock protein 90 mineralocorticoid receptor animal cell article carbamoylation cell membrane permeability cell nucleus controlled study cytoplasm dissociation kidney collecting tubule ligand binding mouse nonhuman nuclear localization signal priority journal protein localization rat Active Transport, Cell Nucleus Aldosterone Animals HSP90 Heat-Shock Proteins Kidney Kinetics Nuclear Localization Signals Rats Receptors, Mineralocorticoid Rattus |
| spellingShingle |
Antibodies Biological organs Cells Chemical bonds Dissociation Hormones Proteins Glucocorticoid receptors Mineralocorticoid receptor (MR) Nuclear accumulation Nuclear localization signals (NLS) Neurology aldosterone corticosteroid receptor digitonin heat shock protein 90 mineralocorticoid receptor animal cell article carbamoylation cell membrane permeability cell nucleus controlled study cytoplasm dissociation kidney collecting tubule ligand binding mouse nonhuman nuclear localization signal priority journal protein localization rat Active Transport, Cell Nucleus Aldosterone Animals HSP90 Heat-Shock Proteins Kidney Kinetics Nuclear Localization Signals Rats Receptors, Mineralocorticoid Rattus Pilipuk, G.P. Vinson, G.P. Sanchez, C.G. Galigniana, M.D. Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor |
| topic_facet |
Antibodies Biological organs Cells Chemical bonds Dissociation Hormones Proteins Glucocorticoid receptors Mineralocorticoid receptor (MR) Nuclear accumulation Nuclear localization signals (NLS) Neurology aldosterone corticosteroid receptor digitonin heat shock protein 90 mineralocorticoid receptor animal cell article carbamoylation cell membrane permeability cell nucleus controlled study cytoplasm dissociation kidney collecting tubule ligand binding mouse nonhuman nuclear localization signal priority journal protein localization rat Active Transport, Cell Nucleus Aldosterone Animals HSP90 Heat-Shock Proteins Kidney Kinetics Nuclear Localization Signals Rats Receptors, Mineralocorticoid Rattus |
| description |
In the absence of hormone, corticosteroid receptors are primarily located in the cytoplasm, and they rapidly accumulate in the nucleus (t0.5 = 5 min) upon ligand binding. It is generally believed that the dissociation of hsp90 from the receptor is an absolute requirement for allowing its nuclear translocation. However, recent evidence suggests that hsp90 may remain associated with the glucocorticoid receptor during this process, and thus, the receptor nuclear localization signal (NLS) is not obscured by its presence. To determine the requirements for mineralocorticoid receptor (MR) nuclear transport, it was first shown that in rat kidney collecting duct cells, nuclear localization of MR in the presence of aldosterone was complete in 10 min. Although the hsp90 inhibitor radicicol delayed nuclear translocation, it did not prevent complete nuclear accumulation of MR at longer incubation times (t 0.5 = 30-40 min). MR carbamylation generates a non-steroid- transformed receptor that, in contrast to native MR, is very stable in cell-free systems. In contrast to the full nuclear translocation of aldosterone- transformed MR, only a fraction of the carbamylated MR became nuclear in digitonin-permeabilized cells even though its NLS is exposed. Furthermore, while preincubation of permeabilized cells with NL1 peptide or anti-NL1 antibody fully inhibited the nuclear translocation of NL1-tagged albumin, neither treatment fully inhibited MR nuclear translocation. We postulate that there are at least two possible mechanisms for MR nuclear translocation. One of them is hsp90- and NL1-dependent, and the other functions in a manner that is independent of the classical pathway. © 2007 American Chemical Society. |
| format |
JOUR |
| author |
Pilipuk, G.P. Vinson, G.P. Sanchez, C.G. Galigniana, M.D. |
| author_facet |
Pilipuk, G.P. Vinson, G.P. Sanchez, C.G. Galigniana, M.D. |
| author_sort |
Pilipuk, G.P. |
| title |
Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor |
| title_short |
Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor |
| title_full |
Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor |
| title_fullStr |
Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor |
| title_full_unstemmed |
Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor |
| title_sort |
evidence for nl1-independent nuclear translocation of the mineralocorticoid receptor |
| url |
http://hdl.handle.net/20.500.12110/paper_00062960_v46_n5_p1389_Pilipuk |
| work_keys_str_mv |
AT pilipukgp evidencefornl1independentnucleartranslocationofthemineralocorticoidreceptor AT vinsongp evidencefornl1independentnucleartranslocationofthemineralocorticoidreceptor AT sanchezcg evidencefornl1independentnucleartranslocationofthemineralocorticoidreceptor AT galignianamd evidencefornl1independentnucleartranslocationofthemineralocorticoidreceptor |
| _version_ |
1782026057065431040 |