%0 Journal Article
%A Gavoci, Antoneta
%A Zhiti, Anxhela
%A Rusková, Michaela
%A Magiera, Maria M
%A Wang, Mengzhe
%A Ziegler, Karin A
%A Hausrat, Torben J
%A Ugwuja, Anselm I
%A Chakraborty, Shreyangi
%A Engelhardt, Stefan
%A Kneussel, Matthias
%A Balastik, Martin
%A Janke, Carsten
%A Misgeld, Thomas
%A Brill, Monika S
%T Polyglutamylation of microtubules drives neuronal remodeling.
%J Nature Communications
%V 16
%N 1
%@ 2041-1723
%C [London]
%I Springer Nature
%M DZNE-2025-00735
%P 5384
%D 2025
%X 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.
%K Microtubules: metabolism
%K Animals
%K Tubulin: metabolism
%K Peptide Synthases: metabolism
%K Peptide Synthases: genetics
%K Motor Neurons: metabolism
%K Hippocampus: metabolism
%K Hippocampus: cytology
%K Neuronal Plasticity: physiology
%K Synapses: metabolism
%K Synaptic Transmission
%K Neurons: metabolism
%K Polyglutamic Acid: metabolism
%K Neuromuscular Junction: metabolism
%K Protein Processing, Post-Translational
%K Mice
%K Spastin: metabolism
%K Tubulin (NLM Chemicals)
%K Peptide Synthases (NLM Chemicals)
%K tubulin polyglutamylase (NLM Chemicals)
%K Polyglutamic Acid (NLM Chemicals)
%K Spastin (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40562742
%2 pmc:PMC12198417
%R 10.1038/s41467-025-60855-6
%U https://pub.dzne.de/record/279358