Membrane interactions and fibrillization of α-synuclein play an essential role in membrane disruption

Himanshu Chaudhary, Anja N D Stefanovic, V Subramaniam, Mireille M A E Claessens

    Research output: Contribution to JournalArticleAcademicpeer-review

    Abstract

    We studied α-synuclein (αS) aggregation in giant vesicles, and observed dramatic membrane disintegration, as well as lipid incorporation into micrometer-sized suprafibrillar aggregates. In the presence of dye-filled vesicles, dye leakage and fibrillization happen concurrently. However, growing fibrils do not impair the integrity of phospholipid vesicles that have a low affinity for αS. Seeding αS aggregation accelerates dye leakage, indicating that oligomeric species are not required to explain the observed effect. The evolving picture suggests that fibrils that appear in solution bind membranes and recruit membrane-bound monomers, resulting in lipid extraction, membrane destabilization and the formation of lipid-containing suprafibrillar aggregates.

    Original languageEnglish
    Pages (from-to)4457-4463
    Number of pages7
    JournalFEBS Letters
    Volume588
    Issue number23
    Early online date25 Oct 2014
    DOIs
    Publication statusPublished - 28 Nov 2014

    Keywords

    • Cell Membrane
    • Humans
    • Lipid Bilayers
    • Protein Aggregation, Pathological
    • Protein Binding
    • Protein Structure, Secondary
    • alpha-Synuclein
    • Journal Article
    • Research Support, Non-U.S. Gov't

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