ArticleNature communications2025
Polyglutamylation of microtubules drives neuronal remodeling.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- The small giant actor in the pathogenesis of neurodegenerative diseases: Microtubules.Metabolic brain disease · 2026Review
- The deficiency of KIF2C leads to abnormal distribution of cortical neurons and behavioral deficits in mice.iScience · 2026Article
- Article
- Tubulin polyglutamylases TTLL4C and TTLL6B are essential for maintaining cytoskeletal integrity inmSphere · 2026Article
- The Axon as a Self-Modifying Computational System: Autonomous Inference, Adaptive Propagation, and AI-Enabled Mechanistic Insight.International journal of molecular sciences · 2026Review
- Doublecortin restricts neuronal branching by regulating tubulin polyglutamylation.Nature communications · 2025Article
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Authors and funding
15 authors.
Funding
Abstract
Developmental remodeling shapes neural circuits via activity-dependent pruning of synapses and axons. Regulation of the cytoskeleton is critical for this process, as microtubule loss via enzymatic severing is an early step of pruning across many circuits and species. However, how microtubule-severing enzymes, such as spastin, are activated in specific neuronal compartments remains unknown. Here, we reveal that polyglutamylation, a post-translational tubulin modification enriched in neurons, plays an instructive role in developmental remodeling by tagging microtubules for severing. Motor neuron-specific gene deletion of enzymes that add or remove tubulin polyglutamylation-TTLL glutamylases vs. CCP deglutamylases-accelerates or delays neuromuscular synapse remodeling in a neurotransmission-dependent manner. This mechanism is not specific to peripheral synapses but also operates in central circuits, e.g., the hippocampus. Thus, tubulin polyglutamylation acts as a cytoskeletal rheostat of remodeling that shapes neuronal morphology and connectivity.
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Registered trials
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