Subcellular rearrangement of hsp90-binding immunophilins accompanies neuronal differentiation and neurite outgrowth

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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...

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Detalles Bibliográficos
Autores principales: Quintá, H.R., Maschi, D., Gomez-Sanchez, C., Piwien-Pilipuk, G., Galigniana, M.D.
Formato: Artículo publishedVersion
Lenguaje:Inglés
Publicado: 2010
Materias:
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
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_00223042_v115_n3_p716_Quinta
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
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.

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