Cholesterol facilitates interactions between α-synuclein oligomers and charge-neutral membranes

TY - JOUR

T1 - Cholesterol facilitates interactions between α-synuclein oligomers and charge-neutral membranes

AU - van Maarschalkerweerd, Andreas

AU - Vetri, Valeria

AU - Vestergaard, Bente

N1 - Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

PY - 2015/9/14

Y1 - 2015/9/14

N2 - Oligomeric species formed during α-synuclein fibrillation are suggested to be membrane-disrupting agents, and have been associated with cytotoxicity in Parkinson's disease. The majority of studies, however, have revealed that the effect of α-synuclein oligomers is only noticeable on systems composed of anionic lipids, while the more physiologically relevant zwitterionic lipids remain intact. We present experimental evidence for significant morphological changes in zwitterionic membranes containing cholesterol, induced by α-synuclein oligomers. Depending on the lipid composition, model membranes are either unperturbed, disrupt, or undergo dramatic morphological changes and segregate into structurally different components, which we visualize by 2-photon fluorescence microscopy and generalized polarization analysis using the fluorescent probe Laurdan. Our results highlight the crucial role of cholesterol for mediating interactions between physiologically relevant membranes and α-synuclein.

AB - Oligomeric species formed during α-synuclein fibrillation are suggested to be membrane-disrupting agents, and have been associated with cytotoxicity in Parkinson's disease. The majority of studies, however, have revealed that the effect of α-synuclein oligomers is only noticeable on systems composed of anionic lipids, while the more physiologically relevant zwitterionic lipids remain intact. We present experimental evidence for significant morphological changes in zwitterionic membranes containing cholesterol, induced by α-synuclein oligomers. Depending on the lipid composition, model membranes are either unperturbed, disrupt, or undergo dramatic morphological changes and segregate into structurally different components, which we visualize by 2-photon fluorescence microscopy and generalized polarization analysis using the fluorescent probe Laurdan. Our results highlight the crucial role of cholesterol for mediating interactions between physiologically relevant membranes and α-synuclein.

KW - 2-Naphthylamine

KW - Cell Membrane

KW - Cholesterol

KW - Fluorescent Dyes

KW - Laurates

KW - Protein Binding

KW - Protein Multimerization

KW - Protein Structure, Secondary

KW - alpha-Synuclein

U2 - 10.1016/j.febslet.2015.08.013

DO - 10.1016/j.febslet.2015.08.013

M3 - Journal article

C2 - 26297828

SN - 0014-5793

VL - 589

SP - 2661

EP - 2667

JO - FEBS Letters

JF - FEBS Letters

IS - 19 Pt B

ER -