Evidence for glucocorticoid receptor transport on microtubules by dynein

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Rapid, ligand-dependent movement of glucocorticoid receptors (GR) from cytoplasm to the nucleus is hsp90-dependent, and much of the movement system has been defined. GR-hsp90 heterocomplexes isolated from cells contain one of several hsp90-binding immunophilins that link the complex to cytoplasmic d...

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Autores principales:	Harrell, J.M., Murphy, P.J.M., Morishima, Y., Chen, H., Mansfield, J.F., Galigniana, M.D., Pratt, W.B.
Formato:	JOUR
Materias:	Binding energy Biochemistry Immunology Cytoplasm Glucocorticoid receptors (GR) Immunophilins Steroids Cells cell protein dynactin dynamitin dynein adenosine triphosphatase glucocorticoid receptor guanosine triphosphate heat shock protein 90 immunophilin molecular motor paclitaxel steroid receptor tubulin unclassified drug animal cell article cell nucleus controlled study cytoplasm dissociation gene overexpression microtubule mouse nonhuman priority journal protein assembly protein transport Animals Antibodies, Monoclonal Binding Sites Biological Transport Cell Line Cell Nucleus Dynein ATPase Fluorescent Antibody Technique Gene Expression Guanosine Triphosphate HSP90 Heat-Shock Proteins Immunosorbent Techniques Kinetics Mice Microscopy, Atomic Force Microtubule-Associated Proteins Microtubules Models, Molecular NIH 3T3 Cells Paclitaxel Rabbits Rats Receptors, Glucocorticoid Transfection Tubulin Animalia
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00219258_v279_n52_p54647_Harrell
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_00219258_v279_n52_p54647_Harrell2023-10-03T14:23:06Z Evidence for glucocorticoid receptor transport on microtubules by dynein Harrell, J.M. Murphy, P.J.M. Morishima, Y. Chen, H. Mansfield, J.F. Galigniana, M.D. Pratt, W.B. Binding energy Biochemistry Immunology Cytoplasm Glucocorticoid receptors (GR) Immunophilins Steroids Cells cell protein dynactin dynamitin dynein adenosine triphosphatase glucocorticoid receptor guanosine triphosphate heat shock protein 90 immunophilin molecular motor paclitaxel steroid receptor tubulin unclassified drug animal cell article cell nucleus controlled study cytoplasm dissociation gene overexpression microtubule mouse nonhuman priority journal protein assembly protein transport Animals Antibodies, Monoclonal Binding Sites Biological Transport Cell Line Cell Nucleus Cytoplasm Dynein ATPase Fluorescent Antibody Technique Gene Expression Guanosine Triphosphate HSP90 Heat-Shock Proteins Immunophilins Immunosorbent Techniques Kinetics Mice Microscopy, Atomic Force Microtubule-Associated Proteins Microtubules Models, Molecular NIH 3T3 Cells Paclitaxel Rabbits Rats Receptors, Glucocorticoid Transfection Tubulin Animalia Rapid, ligand-dependent movement of glucocorticoid receptors (GR) from cytoplasm to the nucleus is hsp90-dependent, and much of the movement system has been defined. GR-hsp90 heterocomplexes isolated from cells contain one of several hsp90-binding immunophilins that link the complex to cytoplasmic dynein, a molecular motor that processes along microtubular tracks to the nucleus. The immunophilins link to dynein indirectly via the dynamitin component of the dynein-associated dynactin complex (Galigniana, M. D., Harrell, J. M., O'Hagen, H. M., Ljungman, M., and Pratt, W. B. (2004) J. Biol. Chem. 279, 22483-22489). Although it is known that rapid, hsp90-dependent GR movement requires intact microtubules, it has not been shown that the movement is dynein-dependent. Here, we show that overexpression of dynamitin, which blocks movement by dissociating the dynein motor from its cargo, inhibits ligand-dependent movement of the GR to the nucleus. We show that native GR·hsp90·immnunophilin complexes contain dynamitin as well as dynein and that GR heterocomplexes isolated from cytosol containing paclitaxel and GTP to stabilize microtubules also contain tubulin. The complete movement system, including the dynein motor complex and tubulin, can be assembled under cell-free conditions by incubating GR immune pellets with paclitaxel/GTP-stabilized cytosol prepared from GR - L cells. This is the first evidence that the movement of a steroid receptor is dynein-dependent, and it is the first isolation of a steroid receptor bound to the entire system that determines its retrograde movement. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00219258_v279_n52_p54647_Harrell
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Binding energy Biochemistry Immunology Cytoplasm Glucocorticoid receptors (GR) Immunophilins Steroids Cells cell protein dynactin dynamitin dynein adenosine triphosphatase glucocorticoid receptor guanosine triphosphate heat shock protein 90 immunophilin molecular motor paclitaxel steroid receptor tubulin unclassified drug animal cell article cell nucleus controlled study cytoplasm dissociation gene overexpression microtubule mouse nonhuman priority journal protein assembly protein transport Animals Antibodies, Monoclonal Binding Sites Biological Transport Cell Line Cell Nucleus Cytoplasm Dynein ATPase Fluorescent Antibody Technique Gene Expression Guanosine Triphosphate HSP90 Heat-Shock Proteins Immunophilins Immunosorbent Techniques Kinetics Mice Microscopy, Atomic Force Microtubule-Associated Proteins Microtubules Models, Molecular NIH 3T3 Cells Paclitaxel Rabbits Rats Receptors, Glucocorticoid Transfection Tubulin Animalia
spellingShingle	Binding energy Biochemistry Immunology Cytoplasm Glucocorticoid receptors (GR) Immunophilins Steroids Cells cell protein dynactin dynamitin dynein adenosine triphosphatase glucocorticoid receptor guanosine triphosphate heat shock protein 90 immunophilin molecular motor paclitaxel steroid receptor tubulin unclassified drug animal cell article cell nucleus controlled study cytoplasm dissociation gene overexpression microtubule mouse nonhuman priority journal protein assembly protein transport Animals Antibodies, Monoclonal Binding Sites Biological Transport Cell Line Cell Nucleus Cytoplasm Dynein ATPase Fluorescent Antibody Technique Gene Expression Guanosine Triphosphate HSP90 Heat-Shock Proteins Immunophilins Immunosorbent Techniques Kinetics Mice Microscopy, Atomic Force Microtubule-Associated Proteins Microtubules Models, Molecular NIH 3T3 Cells Paclitaxel Rabbits Rats Receptors, Glucocorticoid Transfection Tubulin Animalia Harrell, J.M. Murphy, P.J.M. Morishima, Y. Chen, H. Mansfield, J.F. Galigniana, M.D. Pratt, W.B. Evidence for glucocorticoid receptor transport on microtubules by dynein
topic_facet	Binding energy Biochemistry Immunology Cytoplasm Glucocorticoid receptors (GR) Immunophilins Steroids Cells cell protein dynactin dynamitin dynein adenosine triphosphatase glucocorticoid receptor guanosine triphosphate heat shock protein 90 immunophilin molecular motor paclitaxel steroid receptor tubulin unclassified drug animal cell article cell nucleus controlled study cytoplasm dissociation gene overexpression microtubule mouse nonhuman priority journal protein assembly protein transport Animals Antibodies, Monoclonal Binding Sites Biological Transport Cell Line Cell Nucleus Cytoplasm Dynein ATPase Fluorescent Antibody Technique Gene Expression Guanosine Triphosphate HSP90 Heat-Shock Proteins Immunophilins Immunosorbent Techniques Kinetics Mice Microscopy, Atomic Force Microtubule-Associated Proteins Microtubules Models, Molecular NIH 3T3 Cells Paclitaxel Rabbits Rats Receptors, Glucocorticoid Transfection Tubulin Animalia
description	Rapid, ligand-dependent movement of glucocorticoid receptors (GR) from cytoplasm to the nucleus is hsp90-dependent, and much of the movement system has been defined. GR-hsp90 heterocomplexes isolated from cells contain one of several hsp90-binding immunophilins that link the complex to cytoplasmic dynein, a molecular motor that processes along microtubular tracks to the nucleus. The immunophilins link to dynein indirectly via the dynamitin component of the dynein-associated dynactin complex (Galigniana, M. D., Harrell, J. M., O'Hagen, H. M., Ljungman, M., and Pratt, W. B. (2004) J. Biol. Chem. 279, 22483-22489). Although it is known that rapid, hsp90-dependent GR movement requires intact microtubules, it has not been shown that the movement is dynein-dependent. Here, we show that overexpression of dynamitin, which blocks movement by dissociating the dynein motor from its cargo, inhibits ligand-dependent movement of the GR to the nucleus. We show that native GR·hsp90·immnunophilin complexes contain dynamitin as well as dynein and that GR heterocomplexes isolated from cytosol containing paclitaxel and GTP to stabilize microtubules also contain tubulin. The complete movement system, including the dynein motor complex and tubulin, can be assembled under cell-free conditions by incubating GR immune pellets with paclitaxel/GTP-stabilized cytosol prepared from GR - L cells. This is the first evidence that the movement of a steroid receptor is dynein-dependent, and it is the first isolation of a steroid receptor bound to the entire system that determines its retrograde movement.
format	JOUR
author	Harrell, J.M. Murphy, P.J.M. Morishima, Y. Chen, H. Mansfield, J.F. Galigniana, M.D. Pratt, W.B.
author_facet	Harrell, J.M. Murphy, P.J.M. Morishima, Y. Chen, H. Mansfield, J.F. Galigniana, M.D. Pratt, W.B.
author_sort	Harrell, J.M.
title	Evidence for glucocorticoid receptor transport on microtubules by dynein
title_short	Evidence for glucocorticoid receptor transport on microtubules by dynein
title_full	Evidence for glucocorticoid receptor transport on microtubules by dynein
title_fullStr	Evidence for glucocorticoid receptor transport on microtubules by dynein
title_full_unstemmed	Evidence for glucocorticoid receptor transport on microtubules by dynein
title_sort	evidence for glucocorticoid receptor transport on microtubules by dynein
url	http://hdl.handle.net/20.500.12110/paper_00219258_v279_n52_p54647_Harrell
work_keys_str_mv	AT harrelljm evidenceforglucocorticoidreceptortransportonmicrotubulesbydynein AT murphypjm evidenceforglucocorticoidreceptortransportonmicrotubulesbydynein AT morishimay evidenceforglucocorticoidreceptortransportonmicrotubulesbydynein AT chenh evidenceforglucocorticoidreceptortransportonmicrotubulesbydynein AT mansfieldjf evidenceforglucocorticoidreceptortransportonmicrotubulesbydynein AT galignianamd evidenceforglucocorticoidreceptortransportonmicrotubulesbydynein AT prattwb evidenceforglucocorticoidreceptortransportonmicrotubulesbydynein
_version_	1782026295243177984

Evidence for glucocorticoid receptor transport on microtubules by dynein

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