ArticleMolecular biology of the cell2019
Regulatory mechanisms for the axonal localization of tau protein in neurons.
Article in Molecular biology of the cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 48 citations in OpenAlex.
- Active transport by cytoplasmic dynein sustains dendritic MAP2 localization in developing neurons.The Journal of biological chemistry · 2026Article
- Epitranscriptomic imprints on glial cell polarization: METTL3/IGF2BP2 axis as a driver of neurodegeneration in Alzheimer's disease.Psychopharmacology · 2026Review
- Dexmedetomidine Exerts Multi-level Effects to Ameliorate Alzheimer's Disease Pathology in the Adult Zebrafish Brain.Molecular neurobiology · 2026Article
- Axonopathy: mechanisms and potential therapeutic targets for neurodegenerative diseases.Translational neurodegeneration · 2026Review
- Context-tuned strategies for marker selection precision in neuronal studies.Frontiers in neuroscience · 2026Review
- 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
- ZipAEr: A compressive convolutional autoencoder for high-dimensional spatial omics data at subcellular resolution.Research square · 2025Article
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- α-synuclein and tau: interactions, cross-seeding, and the redefinition of synucleinopathies as complex proteinopathies.Frontiers in neuroscience · 2025Review
- The role of protein phosphorylation modifications mediated by iron metabolism regulatory networks in the pathogenesis of Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
- Effects of an OX2R agonist on migration and removal of tau from mouse brain.Scientific reports · 2024Article
- Overlaps and divergences between tauopathies and synucleinopathies: a duet of neurodegeneration.Translational neurodegeneration · 2024Review
- Neuronal ageing is promoted by the decay of the microtubule cytoskeleton.PLoS biology · 2024Article
- Activation of transient receptor potential vanilloid 1 ameliorates tau accumulation-induced synaptic damage and cognitive dysfunction via autophagy enhancement.CNS neuroscience & therapeutics · 2024Article
- A novelFrontiers in neurology · 2024Article
- Tracking Tau in Neurons: How to Grow, Fix, and Stain Primary Neurons for the Investigation of Tau in All Developmental Stages.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Laser-Induced Axotomy of Human iPSC-Derived and Murine Primary Neurons Decreases Somatic Tau and AT8 Tau Phosphorylation: A Single-Cell Approach to Study Effects of Acute Axonal Damage.Cellular and molecular neurobiology · 2023Article
- All the Tau We Cannot See.Annual review of medicine · 2023Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tau is a microtubule (MT)-associated protein that is thought to be localized to the axon. However, its precise localization in developing neurons and mechanisms for the axonal localization have not been fully addressed. In this study, we found that the axonal localization of tau in cultured rat hippocampal neurons mainly occur during early neuronal development. Interestingly, transient expression of human tau in very immature neurons, but not in mature neurons, mimicked the developmental localization of endogenous tau to the axon. We therefore were able to establish an experimental model, in which exogenously expressed tau can be properly localized to the axon. Using this model, we obtained a surprising finding that the axonal localization of tau did not require stable MT binding. Tau lacking the MT-binding domain (MTBD) exhibited high diffusivity but localized properly to the axon. In contrast, a dephosphorylation-mimetic mutant of the proline-rich region 2 showed reinforced MT binding and mislocalization. Our results suggest that tight binding to MTs prevents tau from entering the axon and results in mislocalization in the soma and dendrites when expressed in mature neurons. This study therefore provides a novel mechanism independent of MTBD for the axonal localization of tau.
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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.