ArticleThe Journal of biological chemistry2017
Axodendritic sorting and pathological missorting of Tau are isoform-specific and determined by axon initial segment architecture.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 151 citations in OpenAlex.
- The PINK1-VCP-p47 pathway protects against tau-induced dendritic shrinkage in cortical neurons through interaction with STIP1.Neurobiology of disease · 2026Article
- Targeting TTLL1 Alleviates Aβ-Induced Microtubule Disruption and TAU Pathology in Human iPSC-Derived Cortical Neurons.Pharmaceutics · 2026Article
- Abl kinase activation promotes axon initial segment disassembly and protein sorting defects in Alzheimer's disease.BMC biology · 2026Article
- Axon Initial Segment: Structure, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Altered trafficking of Kv1-Kvβ2 leads to neuronal hyperexcitability and memory deficits in amyloid-β pathology.Molecular neurodegeneration · 2026Article
- Drosophila wing is a high-throughput and versatile screening tool for Tau-mediated disease mechanisms and drug discovery.Disease models & mechanisms · 2026Article
- Tau Axonal Sorting and Interaction With Synaptic Plasticity Modulators Is Domain- and Isoform-Dependent in Human iPSC-Derived Neurons.Aging cell · 2025Article
- Lamotrigine Restores Impairments in Theta Rhythms and LTP as Early Biomarkers of AβAging and disease · 2025Article
- Tau-Targeted Therapeutic Strategies: Mechanistic Targets, Clinical Pipelines, and Analysis of Failures.Cells · 2025Review
- Role of LIMK1-cofilin-actin axis in dendritic spine dynamics in Alzheimer's disease.Cell death & disease · 2025Review
- Directionality bias underpins divergent spatiotemporal progression of Alzheimer-related tauopathy in mouse models.Alzheimer's & dementia : the journal of the Alzheimer's Association · 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
- A network-level transport model of tau progression in the Alzheimer's brain.Mathematical medicine and biology : a journal of the IMA · 2025Article
- Article
- α-synuclein and tau: interactions, cross-seeding, and the redefinition of synucleinopathies as complex proteinopathies.Frontiers in neuroscience · 2025Review
- Super-resolution imaging of the neuronal cytoskeleton.Npj imaging · 2024Review
- Cellular and pathological functions of tau.Nature reviews. Molecular cell biology · 2024Review
- Suppression of mature TAU isoforms prevents Alzheimer's disease-like amyloid-beta oligomer-induced spine loss in rodent neurons.Neural regeneration research · 2024Article
- Complicated Role of Post-translational Modification and Protease-Cleaved Fragments of Tau in Alzheimer's Disease and Other Tauopathies.Molecular neurobiology · 2024Review
- The six brain-specific TAU isoforms and their role in Alzheimer's disease and related neurodegenerative dementia syndromes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
20 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Subcellular mislocalization of the microtubule-associated protein Tau is a hallmark of Alzheimer disease (AD) and other tauopathies. Six Tau isoforms, differentiated by the presence or absence of a second repeat or of N-terminal inserts, exist in the human CNS, but their physiological and pathological differences have long remained elusive. Here, we investigated the properties and distributions of human and rodent Tau isoforms in primary forebrain rodent neurons. We found that the Tau diffusion barrier (TDB), located within the axon initial segment (AIS), controls retrograde (axon-to-soma) and anterograde (soma-to-axon) traffic of Tau. Tau isoforms without the N-terminal inserts were sorted efficiently into the axon. However, the longest isoform (2N4R-Tau) was partially retained in cell bodies and dendrites, where it accelerated spine and dendrite growth. The TDB (located within the AIS) was impaired when AIS components (ankyrin G, EB1) were knocked down or when glycogen synthase kinase-3β (GSK3β; an AD-associated kinase tethered to the AIS) was overexpressed. Using superresolution nanoscopy and live-cell imaging, we observed that microtubules within the AIS appeared highly dynamic, a feature essential for the TDB. Pathomechanistically, amyloid-β insult caused cofilin activation and F-actin remodeling and decreased microtubule dynamics in the AIS. Concomitantly with these amyloid-β-induced disruptions, the AIS/TDB sorting function failed, causing AD-like Tau missorting. In summary, we provide evidence that the human and rodent Tau isoforms differ in axodendritic sorting and amyloid-β-induced missorting and that the axodendritic distribution of Tau depends on AIS integrity.
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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.