Home > Publications Database > Polyglutamylation of microtubules drives neuronal remodeling. > print

001     279358
005     20250713001451.0
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082 _ _ |a 500
100 1 _ |a Gavoci, Antoneta
|0 0000-0002-9985-6508
|b 0
245 _ _ |a Polyglutamylation of microtubules drives neuronal remodeling.
260 _ _ |a [London]
|c 2025
|b Springer Nature
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520 _ _ |a 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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650 _ 7 |a Tubulin
|2 NLM Chemicals
650 _ 7 |a Peptide Synthases
|0 EC 6.3.2.-
|2 NLM Chemicals
650 _ 7 |a tubulin polyglutamylase
|0 EC 6.3.2.-
|2 NLM Chemicals
650 _ 7 |a Polyglutamic Acid
|0 25513-46-6
|2 NLM Chemicals
650 _ 7 |a Spastin
|0 EC 3.6.4.3
|2 NLM Chemicals
650 _ 2 |a Microtubules: metabolism
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Tubulin: metabolism
|2 MeSH
650 _ 2 |a Peptide Synthases: metabolism
|2 MeSH
650 _ 2 |a Peptide Synthases: genetics
|2 MeSH
650 _ 2 |a Motor Neurons: metabolism
|2 MeSH
650 _ 2 |a Hippocampus: metabolism
|2 MeSH
650 _ 2 |a Hippocampus: cytology
|2 MeSH
650 _ 2 |a Neuronal Plasticity: physiology
|2 MeSH
650 _ 2 |a Synapses: metabolism
|2 MeSH
650 _ 2 |a Synaptic Transmission
|2 MeSH
650 _ 2 |a Neurons: metabolism
|2 MeSH
650 _ 2 |a Polyglutamic Acid: metabolism
|2 MeSH
650 _ 2 |a Neuromuscular Junction: metabolism
|2 MeSH
650 _ 2 |a Protein Processing, Post-Translational
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Spastin: metabolism
|2 MeSH
700 1 _ |a Zhiti, Anxhela
|0 0009-0006-2989-8776
|b 1
700 1 _ |a Rusková, Michaela
|b 2
700 1 _ |a Magiera, Maria M
|0 0000-0003-4847-3053
|b 3
700 1 _ |a Wang, Mengzhe
|b 4
700 1 _ |a Ziegler, Karin A
|0 0009-0002-9364-3349
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700 1 _ |a Hausrat, Torben J
|0 0000-0002-5900-0350
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700 1 _ |a Ugwuja, Anselm I
|0 0009-0001-9893-3938
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700 1 _ |a Chakraborty, Shreyangi
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700 1 _ |a Engelhardt, Stefan
|0 0000-0001-5378-8661
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700 1 _ |a Kneussel, Matthias
|0 0000-0003-4900-366X
|b 10
700 1 _ |a Balastik, Martin
|0 0000-0001-5833-9996
|b 11
700 1 _ |a Janke, Carsten
|0 0000-0001-7053-2000
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700 1 _ |a Misgeld, Thomas
|0 P:(DE-2719)2810727
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700 1 _ |a Brill, Monika S
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773 _ _ |a 10.1038/s41467-025-60855-6
|g Vol. 16, no. 1, p. 5384
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|t Nature Communications
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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