Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-11-2
pubmed:abstractText
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 hormone-dependent 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 ?III-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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1471-4159
pubmed:author
pubmed:copyrightInfo
© 2010 The Authors. Journal of Neurochemistry © 2010 International Society for Neurochemistry.
pubmed:issnType
Electronic
pubmed:volume
115
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
716-34
pubmed:dateRevised
2011-11-1
pubmed:meshHeading
pubmed-meshheading:20796173-Animals, pubmed-meshheading:20796173-Cell Differentiation, pubmed-meshheading:20796173-Cell Line, Tumor, pubmed-meshheading:20796173-Female, pubmed-meshheading:20796173-Fluorescent Antibody Technique, Indirect, pubmed-meshheading:20796173-HSP90 Heat-Shock Proteins, pubmed-meshheading:20796173-Hippocampus, pubmed-meshheading:20796173-Immunophilins, pubmed-meshheading:20796173-Immunosuppressive Agents, pubmed-meshheading:20796173-Neurites, pubmed-meshheading:20796173-Neuroblastoma, pubmed-meshheading:20796173-Neurons, pubmed-meshheading:20796173-Pregnancy, pubmed-meshheading:20796173-RNA, Messenger, pubmed-meshheading:20796173-Rats, pubmed-meshheading:20796173-Signal Transduction, pubmed-meshheading:20796173-Subcellular Fractions, pubmed-meshheading:20796173-Tacrolimus, pubmed-meshheading:20796173-Tacrolimus Binding Proteins, pubmed-meshheading:20796173-Transfection, pubmed-meshheading:20796173-Uridine Triphosphate
pubmed:year
2010
pubmed:articleTitle
Subcellular rearrangement of hsp90-binding immunophilins accompanies neuronal differentiation and neurite outgrowth.
pubmed:affiliation
Instituto de Biología y Medicina Experimental/CONICET, Buenos Aires, Argentina.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural