 |
Journal articles
Differential Membrane Binding and Seeding of Distinct $\alpha$-Synuclein Fibrillar Polymorphs
Abstract : 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 affecting
neuronal homeostasis through the redistribution of synaptic proteins
Cited literature [71 references]
https://hal-cea.archives-ouvertes.fr/cea-02480815
Contributor : Mehdi Kabani Connect in order to contact the contributor
Submitted on : Wednesday, March 11, 2020 - 4:27:01 PM
Last modification on : Friday, October 15, 2021 - 1:40:09 PM
Long-term archiving on: : Friday, June 12, 2020 - 4:58:55 PM
Contributor : Mehdi Kabani Connect in order to contact the contributor
Submitted on : Wednesday, March 11, 2020 - 4:27:01 PM
Last modification on : Friday, October 15, 2021 - 1:40:09 PM
Long-term archiving on: : Friday, June 12, 2020 - 4:58:55 PM
File
Shrivastava et al Biophys J 20...
Files produced by the author(s)