ArticleNature communications2022
Disruption of tubulin-alpha4a polyglutamylation prevents aggregation of hyper-phosphorylated tau and microglia activation in mice.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Targeting TTLL1 Alleviates Aβ-Induced Microtubule Disruption and TAU Pathology in Human iPSC-Derived Cortical Neurons.Pharmaceutics · 2026Article
- TUBA4A: The Tale of an Unconventional Tubulin.Cytoskeleton (Hoboken, N.J.) · 2026Review
- Tubulin glutamylation: a key regulator of flagella, cilia, centrosomes, and disease pathways.Journal of biomedical science · 2026Review
- Neuroprotective mechanism of hydrogen sulfide in okadaic acid-induced alzheimer-like pathology.GeroScience · 2026Article
- The tubulin code in acute ischemic stroke: post-translational reprogramming of the neuronal cytoskeleton and implications for phase-specific neuroprotection.Frontiers in neuroscience · 2026Review
- Elevated polyglutamylation and tau phosphorylation levels are associated with cognitive impairment at diagnosis in patients with primary central nervous system lymphoma.Alzheimer's research & therapy · 2025Article
- Article
- Polyglutamylation of microtubules drives neuronal remodeling.Nature communications · 2025Article
- Emerging roles for tubulin PTMs in neuronal function and neurodegenerative disease.Current opinion in neurobiology · 2025Review
- Constancy of olfactory cilia in rodents.Chemical senses · 2025Article
- Associations between peripheral nerve stimulation and cognitive performance: insights from healthy individuals and various disease pathologies.Frontiers in aging neuroscience · 2025Review
- TUBA4A downregulation as observed in ALSFrontiers in cellular neuroscience · 2024Article
- Role of tubulin post-translational modifications in peripheral neuropathy.Experimental neurology · 2023Review
- How neurons maintain their axons long-term: an integrated view of axon biology and pathology.Frontiers in neuroscience · 2023Review
- MAPping tubulin mutations.Frontiers in cell and developmental biology · 2023Review
- Novel pathogenic variants in Tubulin Tyrosine Like 5 (Molecular vision · 2023Article
- Chromosome segregation fidelity requires microtubule polyglutamylation by the cancer downregulated enzyme TTLL11.Nature communications · 2022Article
- Monoallelic loss of the F-actin-binding protein radixin facilitates startle reactivity and pre-pulse inhibition in mice.Frontiers in cell and developmental biology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dissociation of hyper-phosphorylated Tau from neuronal microtubules and its pathological aggregates, are hallmarks in the etiology of tauopathies. The Tau-microtubule interface is subject to polyglutamylation, a reversible posttranslational modification, increasing negative charge at tubulin C-terminal tails. Here, we asked whether tubulin polyglutamylation may contribute to Tau pathology in vivo. Since polyglutamylases modify various proteins other than tubulin, we generated a knock-in mouse carrying gene mutations to abolish Tuba4a polyglutamylation in a substrate-specific manner. We found that Tuba4a lacking C-terminal polyglutamylation prevents the binding of Tau and GSK3 kinase to neuronal microtubules, thereby strongly reducing phospho-Tau levels. Notably, crossbreeding of the Tuba4a knock-in mouse with the hTau tauopathy model, expressing a human Tau transgene, reversed hyper-phosphorylation and oligomerization of Tau and normalized microglia activation in brain. Our data highlight tubulin polyglutamylation as a potential therapeutic strategy in fighting tauopathies.
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