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

ABSTRACT: 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.

SUBMITTER: Quinta HR

PROVIDER: S-EPMC2977535 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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

Quintá Héctor R HR Maschi Darío D Gomez-Sanchez Celso C Piwien-Pilipuk Graciela G Galigniana Mario D MD

Journal of neurochemistry 20100928 3

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, ...[more]

PMID: 20796173

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Project description:The topological cues of fibrous scaffolds (in particular extracellular matrix (ECM)-mimetic nanofibers) have already proven to be a powerful tool for influencing neuronal morphology and behavior. Remote photothermal optical treatment provides additional opportunities for neuronal activity regulation. A combination of these approaches can provide "smart" 3D scaffolds for efficient axon guidance and neurite growth. In this study we propose two alternative approaches for obtaining biocompatible photothermal scaffolds: surface coating of nylon nanofibers with light-to-heat converting nanoparticles and nanoparticle incorporation inside the fibers. We have determined photoconversion efficiency of fibrous nanomaterials under near infrared (NIR) irradiation, as well as biocompatible photothermal treatment parameters. We also measured photo-induced intracellular heating upon contact of cells with a plasmonic surface. In the absence of NIR stimulation, our fibrous scaffolds with a fiber diameter of 100 nm induced an increase in the proportion of β3-tubulin positive cells, while thermal stimulation of neuroblastoma cells on nanoparticles-decorated scaffolds enhanced neurite outgrowth and promoted neuronal maturation. We demonstrate that contact guidance decorated fibers can stimulate directional growth of processes of differentiated neural cells. We studied the impact of nanoparticles on the surface of ECM-mimetic scaffolds on neurite elongation and axonal branching of rat hippocampal neurons, both as topographic cues and as local heat sources. We show that decorating the surface of nanofibers with nanoparticles does not affect the orientation of neurites, but leads to strong branching, an increase in the number of neurites per cell, and neurite elongation, which is independent of NIR stimulation. The effect of photothermal stimulation is most pronounced when cultivating neurons on nanofibers with incorporated nanoparticles, as compared to nanoparticle-coated fibers. The resulting light-to-heat converting 3D materials can be used as tools for controlled photothermal neuromodulation and as "smart" materials for reconstructive neurosurgery.

Dataset Information

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

Publications

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

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