Membrane interactions and fibrillization of alpha-synuclein play an essential role in membrane disruption
Publication year
2014Source
FEBS Letters, 588, 23, (2014), pp. 4457-4463ISSN
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Publication type
Article / Letter to editor
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Organization
Tumorimmunology
Journal title
FEBS Letters
Volume
vol. 588
Issue
iss. 23
Page start
p. 4457
Page end
p. 4463
Subject
Radboudumc 2: Cancer development and immune defence RIMLS: Radboud Institute for Molecular Life SciencesAbstract
We studied alpha-synuclein (alphaS) 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 alphaS. Seeding alphaS 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.
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