Interaction of the chaperones alpha B-crystallin and CHIP with fibrillar alpha-synuclein: Effects on internalization by cells and identification of interacting interfaces.

Autor: Bendifallah M; CEA, Institut François Jacob (MIRcen) and CNRS, Laboratory of Neurodegenerative Diseases (U9199), 18 Route du Panorama, 92265, Fontenay-aux-Roses, France., Redeker V; CEA, Institut François Jacob (MIRcen) and CNRS, Laboratory of Neurodegenerative Diseases (U9199), 18 Route du Panorama, 92265, Fontenay-aux-Roses, France., Monsellier E; CEA, Institut François Jacob (MIRcen) and CNRS, Laboratory of Neurodegenerative Diseases (U9199), 18 Route du Panorama, 92265, Fontenay-aux-Roses, France., Bousset L; CEA, Institut François Jacob (MIRcen) and CNRS, Laboratory of Neurodegenerative Diseases (U9199), 18 Route du Panorama, 92265, Fontenay-aux-Roses, France., Bellande T; CEA, Institut François Jacob (MIRcen) and CNRS, Laboratory of Neurodegenerative Diseases (U9199), 18 Route du Panorama, 92265, Fontenay-aux-Roses, France., Melki R; CEA, Institut François Jacob (MIRcen) and CNRS, Laboratory of Neurodegenerative Diseases (U9199), 18 Route du Panorama, 92265, Fontenay-aux-Roses, France. Electronic address: ronald.melki@cnrs.fr.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2020 Jun 30; Vol. 527 (3), pp. 760-769. Date of Electronic Publication: 2020 May 16.
DOI: 10.1016/j.bbrc.2020.04.091
Abstrakt: The spread of fibrillar alpha-synuclein from affected to naïve neuronal cells is thought to contribute to the progression of synucleinopathies. The binding of fibrillar alpha-synuclein to the plasma membrane is key in this process. We and others previously showed that coating fibrillar alpha-synuclein by the molecular chaperone Hsc70 affects fibrils properties. Here we assessed the effect of the two molecular chaperones alpha B-crystallin and CHIP on alpha-synuclein fibrils uptake by Neuro-2a cells. We demonstrate that both chaperones diminish fibrils take up by cells. We identify through a cross-linking and mass spectrometry strategy the interaction interfaces between alpha-synuclein fibrils and alpha B-crystallin or CHIP. Our results open the way for designing chaperone-derived polypeptide binders that interfere with the propagation of pathogenic alpha-synuclein assemblies.
(Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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