%0 Journal Article %T Differential Membrane Binding and Seeding of Distinct $\alpha$-Synuclein Fibrillar Polymorphs %+ Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN) %+ Institut du Fer à Moulin %+ Institut de biologie de l'ENS Paris (IBENS) %A Shrivastava, Amulya Nidhi %A Bousset, Luc %A Renner, Marianne %A Redeker, Virginie %A Savistchenko, Jimmy %A Triller, Antoine %A Melki, Ronald %Z his work was supported by grants from the EC Joint Programme on Neurodegenerative Diseases ( TransPathND , ANR-17-JPCD-0002-02 %Z ANR-11-IDEX-0001-02 PSL Research University %< avec comité de lecture %@ 0006-3495 %J Biophysical Journal %I Biophysical Society %8 2020-01 %D 2020 %R 10.1016/j.bpj.2020.01.022 %M 32059758 %K $\alpha$-Synuclein %K protein-protein interaction %K membrane protein clustering %K seeding %K synaptic function %Z Life Sciences [q-bio] %Z Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] %Z Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] %Z Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]Journal articles %X The aggregation of the protein $\alpha$-Synuclein ($\alpha$-Syn) leads to different synucleinopathies. We recently showed that structurally distinct fibrillar $\alpha$-Synuclein polymorphs trigger either Parkinson’s Disease or Multiple System Atrophy hallmarks in vivo. Here, we establish structural-molecular basis for these observations. We show that distinct fibrillar $\alpha$-Syn polymorphs bind to and cluster differentially at the plasma membrane in both primary neuronal cultures and organotypic hippocampal slice cultures from wild-type mice. We demonstrate $\alpha$ polymorph-dependent and concentration-dependent seeding. We show a polymorph-dependent differential synaptic re-distribution of $\alpha$3-Na$^+$/K$^+$-ATPase, GluA2-AMPA and GluN2B-NMDA receptors but not GluA1-AMPA and mGluR5 receptors. We also demonstrate polymorph-dependent alteration in neuronal network activity upon seeded aggregation of $\alpha$-Syn. Our findings bring new insight into how distinct $\alpha$-Syn polymorphs differentially bind to and seed monomeric $\alpha$-Syn aggregation within neurons, thus affectingneuronal homeostasis through the redistribution of synaptic proteins %G English %2 https://cea.hal.science/cea-02480815/document %2 https://cea.hal.science/cea-02480815/file/Shrivastava%20et%20al%20Biophys%20J%202020.pdf %L cea-02480815 %U https://cea.hal.science/cea-02480815 %~ INSERM %~ CEA %~ ENS-PARIS %~ CNRS %~ OPENAIRE %~ IFM %~ CEA-UPSAY %~ PSL %~ UNIV-PARIS-SACLAY %~ JACOB %~ CEA-DRF %~ SORBONNE-UNIVERSITE %~ SORBONNE-UNIV %~ MIRCEN %~ SU-SCIENCES %~ TEST-HALCNRS %~ ENS-PSL %~ UNIVERSITE-PARIS-SACLAY %~ SU-TI %~ ANR %~ GS-ENGINEERING %~ GS-LIFE-SCIENCES-HEALTH %~ ALLIANCE-SU %~ FRM