ArticleBrain : a journal of neurology2022
Tubulin tyrosination regulates synaptic function and is disrupted in Alzheimer's disease.
Article in Brain : a journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 57 citations in OpenAlex.
- The TyrRS cascade: circadian gating of neuronal DNA repair and its collapse in aging.GeroScience · 2026Review
- Towards a systems-level view of the microtubule cytoskeleton and its functions in physiology and disease.Nature reviews. Molecular cell biology · 2026Review
- Condensation of MATCAP promotes CENP-E-dependent chromosome congression in mitosis.Nature communications · 2026Article
- Kinetochore proteins control microtubule dynamics in postmitotic neurons to regulate the formation of dendritic spines.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Tau oligomerization induces nuclear lamina invagination and chromatin remodeling in Alzheimer's disease.Acta neuropathologica · 2026Article
- Computational perspectives on tubulin E-hook structure and mechanisms.Biophysical reports · 2026Review
- Amyloid Beta Oligomers as Early Triggers of Neuronal Cytoskeleton Dysfunction in Alzheimer's Disease.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Review
- Peptide-based covalent inhibitor of tubulin detyrosination promotes mesenchymal-to-epithelial transition in lung cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Emerging Roles of Tubulin Isoforms and Their Post-Translational Modifications in Microtubule-Based Transport and Cellular Functions.Biomolecules · 2026Review
- Effects of microtubule (de)tyrosination on the morphology and motility of Trypanosoma brucei and cross-talk with polyglutamylation.Biology open · 2025Article
- L-Dopa-modified microtubules lead to synapse instability in cultured neurons: possible implications in Parkinson's disease therapy.NPJ Parkinson's disease · 2025Article
- Paclitaxel neurotoxicity is triggered by epidermal EG5-dependent microtubule fasciculation and X-ROS formation.Research square · 2025Article
- Evolving Insights into Prickle2 in Neurodevelopment and Neurological Disorders.Molecular neurobiology · 2025Review
- A Proteomics Profiling Reveals the Neuroprotective Effects of Melatonin on Exogenous β-amyloid-42 Induced Mitochondrial Impairment, Intracellular β-amyloid Accumulation and Tau Hyperphosphorylation in Human SH-SY5Y Cells.Cell biology international · 2025Article
- Article
- Review
- Emerging roles for tubulin PTMs in neuronal function and neurodegenerative disease.Current opinion in neurobiology · 2025Review
- Understanding retinal tau pathology through functional 2D and 3D iPSC-derived in vitro retinal models.Acta neuropathologica communications · 2025Article
- Unveiling the cell biology of hippocampal neurons with dendritic axon origin.The Journal of cell biology · 2025Article
- Measurements of neurite extension and nucleokinesis in an iPSC-derived model system following microtubule perturbation.Molecular biology of the cell · 2025Article
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Authors and funding
23 authors at 3 institutions in 3 countries.
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Abstract
Microtubules play fundamental roles in the maintenance of neuronal processes and in synaptic function and plasticity. While dynamic microtubules are mainly composed of tyrosinated tubulin, long-lived microtubules contain detyrosinated tubulin, suggesting that the tubulin tyrosination/detyrosination cycle is a key player in the maintenance of microtubule dynamics and neuronal homeostasis, conditions that go awry in neurodegenerative diseases. In the tyrosination/detyrosination cycle, the C-terminal tyrosine of α-tubulin is removed by tubulin carboxypeptidases and re-added by tubulin tyrosine ligase (TTL). Here we show that TTL heterozygous mice exhibit decreased tyrosinated microtubules, reduced dendritic spine density and both synaptic plasticity and memory deficits. We further report decreased TTL expression in sporadic and familial Alzheimer's disease, and reduced microtubule dynamics in human neurons harbouring the familial APP-V717I mutation. Finally, we show that synapses visited by dynamic microtubules are more resistant to oligomeric amyloid-β peptide toxicity and that expression of TTL, by restoring microtubule entry into spines, suppresses the loss of synapses induced by amyloid-β peptide. Together, our results demonstrate that a balanced tyrosination/detyrosination tubulin cycle is necessary for the maintenance of synaptic plasticity, is protective against amyloid-β peptide-induced synaptic damage and that this balance is lost in Alzheimer's disease, providing evidence that defective tubulin retyrosination may contribute to circuit dysfunction during neurodegeneration in Alzheimer's disease.
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