Amyloid oligomerization of the Parkinson's disease related protein α-synuclein impacts on its curvature-membrane sensitivity

Journal of Neurochemistry
J Ignacio GalleaM Soledad Celej

Abstract

The amyloid aggregation of the presynaptic protein α-synuclein (AS) is pathognomonic of Parkinson's disease and other neurodegenerative disorders. Physiologically, AS contributes to synaptic homeostasis by participating in vesicle maintenance, trafficking, and release. Its avidity for highly curved acidic membranes has been related to the distinct chemistry of the N-terminal amphipathic helix adopted upon binding to appropriated lipid interfaces. Pathologically, AS populate a myriad of toxic aggregates ranging from soluble oligomers to insoluble amyloid fibrils. Different gain-of-toxic function mechanisms are linked to prefibrillar oligomers which are considered as the most neurotoxic species. Here, we investigated if amyloid oligomerization could hamper AS function as a membrane curvature sensor. We used fluorescence correlation spectroscopy to quantitatively evaluate the interaction of oligomeric species, produced using a popular method based on lyophilization and rehydration, to lipid vesicles of different curvatures and compositions. We found that AS oligomerization has a profound impact on protein-lipid interaction, altering binding affinity and/or curvature sensitivity depending on membrane composition. Our work provides ...Continue Reading

References

May 23, 1998·The Journal of Biological Chemistry·W S DavidsonJ M George
Sep 29, 1998·Methods in Enzymology·S H WhiteK Hristova
Aug 1, 2000·The Journal of Biological Chemistry·E JoP E Fraser
Apr 5, 2001·Journal of Molecular Biology·D EliezerG Browne
Aug 15, 2001·Biochemistry·V Narayanan, S Scarlata
Mar 20, 2002·Cell Biochemistry and Biophysics·P Schwille
Jul 30, 2003·The Journal of Biological Chemistry·Min ZhuAnthony L Fink
Mar 19, 2004·The Journal of Biological Chemistry·Brigitte NuscherKlaus Beyer
Jul 30, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Doris L FortinRobert H Edwards
Dec 24, 2004·The Journal of Biological Chemistry·Tobias S UlmerRobert L Nussbaum
Jul 16, 2005·Proceedings of the National Academy of Sciences of the United States of America·Arjan QuistRatnesh Lal
Nov 5, 2005·Cell·Sreeganga ChandraThomas C Südhof
Feb 4, 2006·The Journal of Biological Chemistry·Frits Kamp, Klaus Beyer
Mar 4, 2006·FEBS Letters·Masami MasudaMasato Hasegawa
Nov 17, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kristin E LarsenDavid Sulzer
Nov 18, 2006·Cell·Shigeo TakamoriReinhard Jahn
Dec 18, 2007·Journal of Molecular Biology·Martin StöcklAndreas Herrmann
Jan 25, 2008·Nature Reviews. Molecular Cell Biology·Gerrit van MeerGerald W Feigenson
Feb 12, 2008·Biochimica Et Biophysica Acta·Eleni GiannakisKevin J Barnham
Jun 3, 2008·Biophysical Journal·Allison Dickey, Roland Faller
Oct 22, 2008·FEBS Letters·Bart D van RooijenVinod Subramaniam
Dec 11, 2008·Proceedings of the National Academy of Sciences of the United States of America·Christine C JaoRalf Langen
Jun 2, 2009·Journal of Molecular Biology·Christina R BodnerAd Bax
Oct 20, 2009·Journal of Molecular Biology·B D van RooijenV Subramaniam
Nov 6, 2009·Journal of the American Chemical Society·Hai-Young KimMarkus Zweckstetter
May 27, 2010·Annual Review of Cell and Developmental Biology·Pavan K AuluckSusan Lindquist
Aug 28, 2010·Science·Jacqueline BurréThomas C Südhof
Oct 7, 2010·Biophysical Journal·Elizabeth R Middleton, Elizabeth Rhoades
Dec 24, 2010·PloS One·Bart D van RooijenVinod Subramaniam
Mar 29, 2011·Annual Review of Biochemistry·Bruno Antonny
Aug 9, 2011·Biochimica Et Biophysica Acta·Candace M PfefferkornJennifer C Lee
Oct 8, 2011·Journal of the American Chemical Society·Nicholas P ReynoldsStefan Seeger
Feb 10, 2012·The Biochemical Journal·María Soledad CelejVincent Raussens
Dec 21, 2012·Nature Reviews. Neuroscience·Hilal A LashuelEliezer Masliah
Apr 27, 2013·Nature Protocols·Saheeb AhmedReinhard Jahn
Oct 9, 2013·Journal of the American Chemical Society·Zhiping JiangJennifer C Lee
Oct 23, 2013·PloS One·Erik HellstrandEmma Sparr

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Citations

May 21, 2019·Frontiers in Molecular Neuroscience·Eftychia VasiliTiago Fleming Outeiro
Jul 16, 2021·Journal of Chemical Theory and Computation·Kai Steffen Stroh, Herre Jelger Risselada

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