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Clustering of Tau fibrils impairs the synaptic composition of α3‐Na + /K + ‐ ATP ase and AMPA receptors
Author(s) -
Shrivastava Amulya Nidhi,
Redeker Virginie,
Pieri Laura,
Bousset Luc,
Renner Marianne,
Madiona Karine,
MailhesHamon Caroline,
Coens Audrey,
Buée Luc,
Hantraye Philippe,
Triller Antoine,
Melki Ronald
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201899871
Subject(s) - ampa receptor , glioblastoma , physics , philosophy , humanities , receptor , medicine , biology , glutamate receptor , genetics , cancer research
Tau assemblies have prion‐like properties: they propagate from one neuron to another and amplify by seeding the aggregation of endogenous Tau. Although key in prion‐like propagation, the binding of exogenous Tau assemblies to the plasma membrane of naïve neurons is not understood. We report that fibrillar Tau forms clusters at the plasma membrane following lateral diffusion. We found that the fibrils interact with the Na + /K + ‐ ATP ase ( NKA ) and AMPA receptors. The consequence of the clustering is a reduction in the amount of α3‐ NKA and an increase in the amount of GluA2‐ AMPA receptor at synapses. Furthermore, fibrillar Tau destabilizes functional NKA complexes. Tau and α‐synuclein aggregates often co‐exist in patients’ brains. We now show evidences for cross‐talk between these pathogenic aggregates with α‐synuclein fibrils dramatically enhancing fibrillar Tau clustering and synaptic localization. Our results suggest that fibrillar α‐synuclein and Tau cross‐talk at the plasma membrane imbalance neuronal homeostasis.