Subcellular rearrangement of hsp90-binding immunophilins accompanies neuronal differentiation and neurite outgrowth
FKBP51 and FKBP52 (FK506-binding protein 51 and 52) are tetratricopeptide repeat-domain immunophilins belonging to the tetratricopeptide- protein•hsp90•hsp70•p23 heterocomplex bound to steroid receptors. Immunophilins are related to receptor folding, subcellular localization, and hormonedependent tr...
| Autores: | , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2010 |
| País: | Argentina |
| Institución: | Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales |
| Repositorio: | Biblioteca Digital (UBA-FCEN) |
| Idioma: | inglés |
| OAI Identifier: | paperaa:paper_00223042_v115_n3_p716_Quinta |
| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_00223042_v115_n3_p716_Quinta |
| Access Level: | acceso abierto |
| Palabra clave: | Chaperones FKBP Hippocampus P23 Tau Tetratricopeptide proteins beta tubulin beta3 tubulin fk 506 binding protein fk 506 binding protein 51 fk 506 binding protein 52 heat shock protein 70 heat shock protein 90 heat shock protein 90 binding immunophilin immunophilin messenger RNA microtubule associated protein 2 protein p23 tau 1 protein tau protein unclassified drug animal cell article brain nerve cell cell nucleus cell stimulation cellular distribution complex formation controlled study cytoplasm embryo gene overexpression gene silencing hippocampus intermediate filament microtubule mouse nerve cell differentiation nerve ending nerve fiber growth neuroblastoma cell nonhuman phenotype priority journal protein analysis protein assembly protein binding protein expression protein function protein transport rat transcription initiation Animals Cell Differentiation Cell Line, Tumor Female Fluorescent Antibody Technique, Indirect HSP90 Heat-Shock Proteins Immunophilins Immunosuppressive Agents Neurites Neuroblastoma Neurons Pregnancy Rats RNA, Messenger Signal Transduction Subcellular Fractions Tacrolimus Tacrolimus Binding Proteins Transfection Uridine Triphosphate |
| Sumario: | FKBP51 and FKBP52 (FK506-binding protein 51 and 52) are tetratricopeptide repeat-domain immunophilins belonging to the tetratricopeptide- protein•hsp90•hsp70•p23 heterocomplex bound to steroid receptors. Immunophilins are related to receptor folding, subcellular localization, and hormonedependent transcription. Also, they bind the immunosuppressant macrolide FK506, which shows neuroregenerative and neuroprotective actions by a still unknown mechanism. In this study, we demonstrate that in both, undifferentiated neuroblastoma cells and embryonic hippocampal neurons, the FKBP52• hsp90•p23 heterocomplex concentrates in a perinuclear structure. Upon cell stimulation with FK506, this structure disassembles and this perinuclear area becomes transcriptionally active. The acquisition of a neuronal phenotype is accompanied by increased expression of bIII-tubulin, Map-2, Tau-1, but also hsp90, hsp70, p23, and FKBP52. During the early differentiation steps, the perinuclear heterocomplex redistributes along the cytoplasm and nascent neurites, p23 binds to intermediate filaments and microtubules acquired higher filamentary organization. While FKBP52 moves towards neurites and concentrates in arborization bodies and terminal axons, FKBP51, whose expression remains constant, replaces FKBP52 in the perinuclear structure. Importantly, neurite outgrowth is favored by FKBP52 over-expression or FKBP51 knock-down, and is impaired by FKBP52 knock-down or FKBP51 over-expression, indicating that the balance between these FK506-binding proteins plays a key role during the early mechanism of neuronal differentiation. © 2010 The Authors. |
|---|