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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Detalles Bibliográficos
Autores principales: Harrell, J.M., Murphy, P.J.M., Morishima, Y., Chen, H., Mansfield, J.F., Galigniana, M.D., Pratt, W.B.
Formato: Artículo publishedVersion
Lenguaje:Inglés
Publicado: 2004
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
Descripción
Sumario: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.

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