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

doi:10.1016/j.febslet.2014.10.016

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 Journal › Article › Academic › peer-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 language	English
Pages (from-to)	4457-4463
Number of pages	7
Journal	FEBS Letters
Volume	588
Issue number	23
Early online date	25 Oct 2014
DOIs	https://doi.org/10.1016/j.febslet.2014.10.016
Publication status	Published - 28 Nov 2014

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SDG 6 Clean Water and Sanitation

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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10.1016/j.febslet.2014.10.016

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title = "Membrane interactions and fibrillization of α-synuclein play an essential role in membrane disruption",

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.",

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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year = "2014",

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doi = "10.1016/j.febslet.2014.10.016",

language = "English",

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AU - Chaudhary, Himanshu

AU - Stefanovic, Anja N D

AU - Subramaniam, V

AU - Claessens, Mireille M A E

PY - 2014/11/28

Y1 - 2014/11/28

N2 - 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.

AB - 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.

KW - Cell Membrane

KW - Humans

KW - Lipid Bilayers

KW - Protein Aggregation, Pathological

KW - Protein Binding

KW - Protein Structure, Secondary

KW - alpha-Synuclein

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

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DO - 10.1016/j.febslet.2014.10.016

M3 - Article

C2 - 25448986

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EP - 4463

JO - FEBS Letters

JF - FEBS Letters

IS - 23

ER -

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

Abstract

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Keywords

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