ArticleThe Journal of biological chemistry2016
Co-immunoprecipitation with Tau Isoform-specific Antibodies Reveals Distinct Protein Interactions and Highlights a Putative Role for 2N Tau in Disease.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 146 citations in OpenAlex.
- Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer's disease modification.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021Trial
- The role of Annexin A2 in Alzheimer's disease: From cellular functions to therapeutic potential.The FEBS journal · 2026Review
- Metal Binding to Tau Protein: Physiological and Pathological Relevance.Biochemistry · 2026Review
- A critical appraisal of the link between apolipoprotein E and Tau.Current opinion in neurology · 2026Review
- Molecular determinants of the immunomodulatory potentials of a novel bifunctional TGF-β1/PD-L1 fusion protein.Biotechnology letters · 2026Article
- Drosophila wing is a high-throughput and versatile screening tool for Tau-mediated disease mechanisms and drug discovery.Disease models & mechanisms · 2026Article
- Role of Mitochondrial Calcium Dysregulation in Alzheimer's Disease Pathogenesis.Molecular neurobiology · 2025Review
- Tau-Mitochondria Interactions in Neurodegeneration: Mechanisms and Therapeutic Potential.Cellular and molecular neurobiology · 2025Review
- Tau Axonal Sorting and Interaction With Synaptic Plasticity Modulators Is Domain- and Isoform-Dependent in Human iPSC-Derived Neurons.Aging cell · 2025Article
- Temporal Interactome Mapping of Human Tau in Drosophila Reveals Progressive Mitochondrial Engagement and Porin/VDAC1-Dependent Modulation of Toxicity.International journal of molecular sciences · 2025Article
- BioID2-Based Tau Interactome Reveals Novel and Known Protein Interactions Associated with Multiple Cellular Pathways.Journal of proteome research · 2025Article
- Rational Modulation of Liquid-Liquid Phase Separation Offers Novel Ways to Combat Tauopathies.International journal of molecular sciences · 2025Review
- Tau-seed interactome analysis reveals distinct functional signatures in Alzheimer's disease across model systems.bioRxiv : the preprint server for biology · 2025Article
- The interactome of tau phosphorylated at T217 in Alzheimer's disease human brain tissue.Acta neuropathologica · 2025Article
- Cyclophilin D (CypD) ablation prevents neurodegeneration and cognitive damage induced by caspase-3 cleaved tau.Free radical biology & medicine · 2025Article
- The tau isoform 1N4R confers vulnerability of MAPT knockout human iPSC-derived neurons to amyloid beta and phosphorylated tau-induced neuronal dysfunction.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Probe-dependent Proximity Profiling (ProPPr) Uncovers Similarities and Differences in Phospho-Tau-Associated Proteomes Between Tauopathies.Molecular neurodegeneration · 2025Article
- Hippocampal mitophagy alterations in MAPT-associated frontotemporal dementia with parkinsonism.Acta neuropathologica communications · 2025Article
- ProtPipe: A Multifunctional Data Analysis Pipeline for Proteomics and Peptidomics.Genomics, proteomics & bioinformatics · 2025Article
- Describing the diversity ofNPJ dementia · 2025Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alternative splicing generates multiple isoforms of the microtubule-associated protein Tau, but little is known about their specific function. In the adult mouse brain, three Tau isoforms are expressed that contain either 0, 1, or 2 N-terminal inserts (0N, 1N, and 2N). We generated Tau isoform-specific antibodies and performed co-immunoprecipitations followed by tandem mass tag multiplexed quantitative mass spectrometry. We identified novel Tau-interacting proteins of which one-half comprised membrane-bound proteins, localized to the plasma membrane, mitochondria, and other organelles. Tau was also found to interact with proteins involved in presynaptic signal transduction. MetaCore analysis revealed one major Tau interaction cluster that contained 33 Tau pulldown proteins. To explore the pathways in which these proteins are involved, we conducted an ingenuity pathway analysis that revealed two significant overlapping pathways, "cell-to-cell signaling and interaction" and "neurological disease." The functional enrichment tool DAVID showed that in particular the 2N Tau-interacting proteins were specifically associated with neurological disease. Finally, for a subset of Tau interactions (apolipoprotein A1 (apoA1), apoE, mitochondrial creatine kinase U-type, β-synuclein, synaptogyrin-3, synaptophysin, syntaxin 1B, synaptotagmin, and synapsin 1), we performed reverse co-immunoprecipitations, confirming the preferential interaction of specific isoforms. For example, apoA1 displayed a 5-fold preference for the interaction with 2N, whereas β-synuclein showed preference for 0N. Remarkably, a reverse immunoprecipitation with apoA1 detected only the 2N isoform. This highlights distinct protein interactions of the different Tau isoforms, suggesting that they execute different functions in brain tissue.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.