α-Synuclein Senses Lipid Packing Defects and Induces Lateral Expansion of Lipids Leading to Membrane Remodeling
Myriam Ouberai,Juan Wang,Marcus J. Swann,Céline Galvagnion,Tim Guilliams,Christopher M. Dobson,Mark E. Welland +6 more
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TLDR
The ability of α-Syn to sense lipid packing defects and to remodel membrane structure supports its proposed role in vesicle trafficking.About:
This article is published in Journal of Biological Chemistry.The article was published on 2013-07-19 and is currently open access. It has received 181 citations till now. The article focuses on the topics: Lipid bilayer phase behavior & Biological membrane.read more
Citations
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Journal ArticleDOI
The function of α-synuclein.
TL;DR: The role of synuclein at the nerve terminal and in membrane remodeling is reviewed and the prion-like propagation of misfoldedsynuclein is considered as a mechanism for the spread of degeneration through the neuraxis.
Journal ArticleDOI
Lipid vesicles trigger α-synuclein aggregation by stimulating primary nucleation
Céline Galvagnion,Alexander K. Buell,Georg Meisl,Thomas C. T. Michaels,Michele Vendruscolo,Tuomas P. J. Knowles,Christopher M. Dobson +6 more
TL;DR: The results reveal the key role that membrane interactions can have in triggering conversion of α-syn from its soluble state to the aggregated state that is associated with neurodegeneration and to its associated disease states.
Journal ArticleDOI
Structural characterization of toxic oligomers that are kinetically trapped during α-synuclein fibril formation
Serene W. Chen,Srdja Drakulic,Emma Deas,Myriam Ouberai,Francesco A. Aprile,Rocío Arranz,Samuel Ness,Cintia Roodveldt,Tim Guilliams,Erwin J. De-Genst,David Klenerman,Nicholas W. Wood,Tuomas P. J. Knowles,Carlos Alfonso,Germán Rivas,Andrey Y. Abramov,José M. Valpuesta,Christopher M. Dobson,Nunilo Cremades +18 more
TL;DR: The findings reveal the inherent multiplicity of the process of protein misfolding and the key role the β-sheet geometry acquired in the early stages of the self-assembly process plays in dictating the kinetic stability and the pathological nature of individual oligomeric species.
Journal ArticleDOI
α-Synuclein assembles into higher-order multimers upon membrane binding to promote SNARE complex formation
TL;DR: It is shown using chemical cross-linking and fluorescence resonance energy transfer (FRET) that α-synuclein multimerizes into large homomeric complexes upon membrane binding and that the membrane-bound, multimeric form of α- synuclein mediates SNARE complex assembly in presynaptic terminals.
Journal ArticleDOI
The Synaptic Function of α-Synuclein.
TL;DR: This review focuses on the structural characteristics of α-synuclein, its cellular and subcellular localization, and discusses how this relates to its function in neurons, in particular at the neuronal synapse.
References
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Journal ArticleDOI
Alpha-synuclein in Lewy bodies.
Maria Grazia Spillantini,Marie L. Schmidt,Virginia M.-Y. Lee,John Q. Trojanowski,Ross Jakes,Michel Goedert +5 more
TL;DR: Strong staining of Lewy bodies from idiopathic Parkinson's disease with antibodies for α-synuclein, a presynaptic protein of unknown function which is mutated in some familial cases of the disease, indicates that the LewY bodies from these two diseases may have identical compositions.
Journal ArticleDOI
Protein Misfolding, Functional Amyloid, and Human Disease
TL;DR: The relative importance of the common main-chain and side-chain interactions in determining the propensities of proteins to aggregate is discussed and some of the evidence that the oligomeric fibril precursors are the primary origins of pathological behavior is described.
Journal ArticleDOI
Membrane curvature and mechanisms of dynamic cell membrane remodelling
TL;DR: Membrane curvature is no longer seen as a passive consequence of cellular activity but an active means to create membrane domains and to organize centres for membrane trafficking.
Journal ArticleDOI
Stabilization of α-Synuclein Secondary Structure upon Binding to Synthetic Membranes
TL;DR: It is reported that α-synuclein binds to small unilamellarospholipid vesicles containing acidic phospholipids, but not to vesicular charges with a net neutral charge, consistent with a role in vesicle function at the presynaptic terminal.
Journal ArticleDOI
Structure and Dynamics of Micelle-bound Human α-Synuclein
TL;DR: The well ordered conformation of the helix-helix connector indicates a defined interaction with lipidic surfaces, suggesting that, when bound to larger diameter synaptic vesicles, it can act as a switch between this structure and a previously proposed uninterrupted helix.
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