Proteomics

Dataset Information

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Comparative interactome analyses of wild-type and P301L MAPT in two human neuronal cell lines

ABSTRACT: Protein interactions of the tau protein are of interest in efforts to decipher the mechanisms of cell death in Alzheimer Disease (AD), a subset of frontotemporal dementias (FTD) and other tauopathies. We recently reported on extensive interactions of tau with the ribonucleoproteome and chaperones. A confounder of this prior work was that it probed steady-state interactions of plasmid-encoded four-repeat (4R) tau in dividing cells. Since then, we genome-edited a genomic safe harbor locus in two human neuronal cell lines, namely IMR-32 and ReNcell VM, creating inducible EGFP tagged wild-type and P301L tau models. We expressed balanced levels of 3R- and 4R-tau and interrogated tau protein interactions at specific times following its induction. In addition to its association with the ribonucleoproteome, tau was observed to interact in these models with proteins that escaped prior investigations.

INSTRUMENT(S): Orbitrap Fusion ETD

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain, Central Nervous System Neuron, Cell Culture

DISEASE(S): Frontotemporal Dementia,Tauopathy,Alzheimer's Disease

SUBMITTER: Declan Williams  

LAB HEAD: Gerold Schmitt-Ulms

PROVIDER: PXD010040 | Pride | 2019-11-13

REPOSITORIES: Pride

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Publications

Tau interactome analyses in CRISPR-Cas9 engineered neuronal cells reveal ATPase-dependent binding of wild-type but not P301L Tau to non-muscle myosins.

Wang Xinzhu X   Williams Declan D   Müller Iris I   Lemieux Mackenzie M   Dukart Ramona R   Maia Isabella B L IBL   Wang Hansen H   Woerman Amanda L AL   Schmitt-Ulms Gerold G  

Scientific reports 20191107 1

Protein interactions of Tau are of interest in efforts to decipher pathogenesis in Alzheimer's disease, a subset of frontotemporal dementias, and other tauopathies. We CRISPR-Cas9 edited two human cell lines to generate broadly adaptable models for neurodegeneration research. We applied the system to inducibly express balanced levels of 3-repeat and 4-repeat wild-type or P301L mutant Tau. Following 12-h induction, quantitative mass spectrometry revealed the Parkinson's disease-causing protein DJ  ...[more]

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