@article{shrivastava_clustering_2019, title = {Clustering of Tau fibrils impairs the synaptic composition of α3‐Na+/K+‐{ATPase} and {AMPA} receptors}, rights = {© 2019 The Authors. Published under the terms of the {CC} {BY} 4.0 license. This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.}, issn = {0261-4189, 1460-2075}, url = {https://www.embopress.org/doi/full/10.15252/embj.201899871}, doi = {10.15252/embj.201899871}, abstract = {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+‐{ATPase} ({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 {GluA}2‐{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. Synopsis {\textless}img class="highwire-embed" alt="Embedded Image" src="http://emboj.embopress.org/sites/default/files/highwire/embojnl/early/2019/01/08/embj.201899871/embed/graphic-1.gif"/{\textgreater} Pathogenic fibrillar Tau remodel excitatory synaptic protein composition and imbalance neuronal homeostasis. Exogenous fibrillar‐Tau clusters at excitatory synapses.The membrane interactome of fibrillar Tau is identified.Fibrillar‐Tau interacts with Na+/K+‐{ATPase} and {GluA}2‐{AMPA} receptor.Fibrillar Tau reduces Na+/K+‐{ATPase} and increases {GluA}2‐{AMPA} receptor at synapses.Synuclein fibrils cross‐talk with fibrillar‐Tau at neuronal membrane.}, pages = {e99871}, journaltitle = {The {EMBO} Journal}, author = {Shrivastava, Amulya Nidhi and Redeker, Virginie and Pieri, Laura and Bousset, Luc and Renner, Marianne and Madiona, Karine and Mailhes‐Hamon, Caroline and Coens, Audrey and Buée, Luc and Hantraye, Philippe and Triller, Antoine and Melki, Ronald}, urldate = {2019-01-11}, date = {2019-01-08}, langid = {english}, pmid = {30630857}, keywords = {cross‐talk of pathogenic proteins, highlight, misfolding disease, peer-reviewed, protein aggregation and clustering, single‐particle tracking, tauopathies}, }