Although cyclophilin A (CyP-A) is a relatively abundant small immunophilin present in the cytoplasm of all mammalian cells, its general function(s) in the absence of the immunosuppressant drug cyclosporin A is not known. In contrast, the high molecular weight hsp90-binding immunophilins appear to play a role in protein trafficking in that they have been shown to link glucocorticoid receptor-hsp90 and p53-hsp90 complexes to the dynein motor protein for retrograde movement along microtubules. These immunophilins link to cytoplasmic dynein indirectly through the association of the immunophilin peptidylprolyl isomerase (PPIase) domain with dynamitin, a 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). Here, we show that CyP-A exists in native heterocomplexes containing cytoplasmic dynein that can be formed in cell-free systems. Prolyl isomerase activity is not required for forming the dynein complex, but the PPIase domain fragment of FKBP52 blocks complex formation and CyP-A binds to dynamitin in a PPIase domain-dependent manner. CyP-A heterocomplexes containing tubulin and dynein can be formed in cytosol prepared under microtubule-stabilizing conditions, and CyP-A colocalizes in mouse fibroblasts with microtubules. Colocalization with microtubules is disrupted by overexpression of the PPIase domain fragment. Thus, we conclude that CyP-A associates in vitro and in vivo with the dynein/dynactin motor protein complex and we suggest that CyP-A may perform a general function related to the binding of cargo for retrograde movement along microtubules.
Documento: | Artículo |
Título: | Cyclophilin-A is bound through its peptidylprolyl isomerase domain to the cytoplasmic dynein motor protein complex |
Autor: | Galigniana, M.D.; Morishima, Y.; Gallay, P.A.; Pratt, W.B. |
Filiación: | Department of Pharmacology, Univ. of Michigan Medical School, Ann Arbor, MI 48109, United States Department of Immunology, Scripps Research Institute, San Diego, CA 92037, United States Departamento de Quimica Biologica, Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires C1428EGA, Argentina Dept. of Pharmacology, Univ. of Michigan Medical School, 1301 Med. Science Research Bldg. III, Ann Arbor, MI 48109-0632, United States |
Palabras clave: | Cells; Cytology; Drug products; Immunology; Living systems studies; Molecular weight; Immunophilins; Microtubules; Prolyl isomerase; Protein trafficking; Proteins; cyclophilin; cyclophilin A; cyclosporin A; dynein adenosine triphosphatase; heat shock protein 90; immunophilin; immunosuppressive agent; protein p53; tubulin; animal cell; article; complex formation; controlled study; cytoplasm; cytosol; enzyme activity; in vitro study; in vivo study; microtubule; molecular weight; mouse; nonhuman; priority journal; protein binding; protein domain; protein expression; protein function; protein localization; protein protein interaction; protein synthesis; protein transport; Animals; Cell Line; Cell-Free System; Cyclophilin A; Cyclosporine; Cytoplasm; Fluorescent Antibody Technique, Indirect; Glutathione; HSP90 Heat-Shock Proteins; Immunoblotting; Immunosuppressive Agents; Mice; Microtubule-Associated Proteins; Microtubules; NIH 3T3 Cells; Peptidylprolyl Isomerase; Plasmids; Protein Binding; Protein Structure, Tertiary; Rabbits; Receptors, Glucocorticoid; Tumor Suppressor Protein p53; Animalia; Mammalia |
Año: | 2004 |
Volumen: | 279 |
Número: | 53 |
Página de inicio: | 55754 |
Página de fin: | 55759 |
DOI: | http://dx.doi.org/10.1074/jbc.M406259200 |
Título revista: | Journal of Biological Chemistry |
Título revista abreviado: | J. Biol. Chem. |
ISSN: | 00219258 |
CODEN: | JBCHA |
CAS: | cyclophilin, 126043-36-5; cyclosporin A, 59865-13-3, 63798-73-2; Cyclophilin A, EC 5.2.1.-; Cyclosporine, 59865-13-3; dynactin, 144198-36-7; Glutathione, 70-18-8; HSP90 Heat-Shock Proteins; Immunosuppressive Agents; Microtubule-Associated Proteins; Peptidylprolyl Isomerase, EC 5.2.1.8; Receptors, Glucocorticoid; Tumor Suppressor Protein p53 |
PDF: | https://bibliotecadigital.exactas.uba.ar/download/paper/paper_00219258_v279_n53_p55754_Galigniana.pdf |
Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v279_n53_p55754_Galigniana |