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

Maya Bendifallah (1) , Virginie Redeker (1) , Elodie Monsellier (1) , Luc Bousset (1) , Tracy Bellande (1) , Ronald Melki (1)

1 LMN - Laboratoire des Maladies Neurodégénératives - UMR 9199

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.

Domains: Life Sciences [q-bio]; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Biochemistry [q-bio.BM]; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Genomics [q-bio.GN]

Maya Bendifallah, Virginie Redeker, Elodie Monsellier, Luc Bousset, Tracy Bellande, et al.. Interaction of the chaperones alpha B-crystallin and CHIP with fibrillar alpha-synuclein: Effects on internalization by cells and identification of interacting interfaces. Biochemical and Biophysical Research Communications, 2020, ⟨10.1016/j.bbrc.2020.04.091⟩. ⟨cea-02614589⟩