Proteomics

Dataset Information

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Identification of proteins that interact with extracellularly applied fibrillar Tau assemblies


ABSTRACT: The microtubule associated protein Tau (MAPT) expressed in neurons is involved in microtubules stabilization, cell morphogenesis and axonal transport. In pathological conditions, Tau assembles into high molecular weight assemblies leading to neuropathological Tau deposits, the hallmark of several neurodegenerative diseases collectively named “tauopathies”, including Alzheimer’s disease. These pathologic Tau assemblies are released by affected neuronal cells and taken up by naïve neighbor cells, propagate from one cell to another and amplify by seeding the aggregation of endogenous Tau. In order to identify plasma membrane proteins exposed extracellularly that interact with extracellularly applied fibrillar Tau assemblies, we exposed pure-neuronal cultures to fibrillar Tau for 10 min, pulled down the associated proteins, and identified them using a proteomic-based approach. Of the six Tau isoforms produced by alternative splicing of the MAPT gene and differing from each other by the presence or absence of one or two inserts in the N-terminal part (0N, 1N or 2N) of the protein and by the presence of either three or four repeated microtubule binding motifs in the protein C-terminal part (3R or 4R), we have expressed and purified 1N3R and 1N4R Tau isoforms and further assembled them into 1N3R and 1N4R Tau fibrils. Using pull-down of whole cell lysates and mass spectrometry, we have identified proteins interacting with extracellularly applied Tau fibrils. We have performed two different experiments with either 1N3R Tau fibrils or 1N4R Tau fibrils (condition 1 and condition 2 respectively). Each condition consists in six experimental replicates of cells exposed 10 min to Tau fibrils and of the non-treated cells used as controls.

INSTRUMENT(S): TripleTOF 4600

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain, Neuron Of Cerebral Cortex

DISEASE(S): Alzheimer's Disease

SUBMITTER: Virginie Redeker  

LAB HEAD: Ronald Melki, Virginie Redeker

PROVIDER: PXD009294 | Pride | 2019-01-09

REPOSITORIES: Pride

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Publications

Clustering of Tau fibrils impairs the synaptic composition of α3-Na<sup>+</sup>/K<sup>+</sup>-ATPase and AMPA receptors.

Shrivastava Amulya Nidhi AN   Redeker Virginie V   Pieri Laura L   Bousset Luc L   Renner Marianne M   Madiona Karine K   Mailhes-Hamon Caroline C   Coens Audrey A   Buée Luc L   Hantraye Philippe P   Triller Antoine A   Melki Ronald R  

The EMBO journal 20190110 3


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<sup>+</sup>/K<sup>+</sup>-ATPase (NKA) and AMPA receptors. The consequence  ...[more]

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