000279358 001__ 279358 000279358 005__ 20250713001451.0 000279358 0247_ $$2doi$$a10.1038/s41467-025-60855-6 000279358 0247_ $$2pmid$$apmid:40562742 000279358 0247_ $$2pmc$$apmc:PMC12198417 000279358 0247_ $$2altmetric$$aaltmetric:178347251 000279358 037__ $$aDZNE-2025-00735 000279358 041__ $$aEnglish 000279358 082__ $$a500 000279358 1001_ $$00000-0002-9985-6508$$aGavoci, Antoneta$$b0 000279358 245__ $$aPolyglutamylation of microtubules drives neuronal remodeling. 000279358 260__ $$a[London]$$bSpringer Nature$$c2025 000279358 3367_ $$2DRIVER$$aarticle 000279358 3367_ $$2DataCite$$aOutput Types/Journal article 000279358 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1752047021_8072 000279358 3367_ $$2BibTeX$$aARTICLE 000279358 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000279358 3367_ $$00$$2EndNote$$aJournal Article 000279358 520__ $$aDevelopmental 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. 000279358 536__ $$0G:(DE-HGF)POF4-351$$a351 - Brain Function (POF4-351)$$cPOF4-351$$fPOF IV$$x0 000279358 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 000279358 650_7 $$2NLM Chemicals$$aTubulin 000279358 650_7 $$0EC 6.3.2.-$$2NLM Chemicals$$aPeptide Synthases 000279358 650_7 $$0EC 6.3.2.-$$2NLM Chemicals$$atubulin polyglutamylase 000279358 650_7 $$025513-46-6$$2NLM Chemicals$$aPolyglutamic Acid 000279358 650_7 $$0EC 3.6.4.3$$2NLM Chemicals$$aSpastin 000279358 650_2 $$2MeSH$$aMicrotubules: metabolism 000279358 650_2 $$2MeSH$$aAnimals 000279358 650_2 $$2MeSH$$aTubulin: metabolism 000279358 650_2 $$2MeSH$$aPeptide Synthases: metabolism 000279358 650_2 $$2MeSH$$aPeptide Synthases: genetics 000279358 650_2 $$2MeSH$$aMotor Neurons: metabolism 000279358 650_2 $$2MeSH$$aHippocampus: metabolism 000279358 650_2 $$2MeSH$$aHippocampus: cytology 000279358 650_2 $$2MeSH$$aNeuronal Plasticity: physiology 000279358 650_2 $$2MeSH$$aSynapses: metabolism 000279358 650_2 $$2MeSH$$aSynaptic Transmission 000279358 650_2 $$2MeSH$$aNeurons: metabolism 000279358 650_2 $$2MeSH$$aPolyglutamic Acid: metabolism 000279358 650_2 $$2MeSH$$aNeuromuscular Junction: metabolism 000279358 650_2 $$2MeSH$$aProtein Processing, Post-Translational 000279358 650_2 $$2MeSH$$aMice 000279358 650_2 $$2MeSH$$aSpastin: metabolism 000279358 7001_ $$00009-0006-2989-8776$$aZhiti, Anxhela$$b1 000279358 7001_ $$aRusková, Michaela$$b2 000279358 7001_ $$00000-0003-4847-3053$$aMagiera, Maria M$$b3 000279358 7001_ $$aWang, Mengzhe$$b4 000279358 7001_ $$00009-0002-9364-3349$$aZiegler, Karin A$$b5 000279358 7001_ $$00000-0002-5900-0350$$aHausrat, Torben J$$b6 000279358 7001_ $$00009-0001-9893-3938$$aUgwuja, Anselm I$$b7 000279358 7001_ $$aChakraborty, Shreyangi$$b8 000279358 7001_ $$00000-0001-5378-8661$$aEngelhardt, Stefan$$b9 000279358 7001_ $$00000-0003-4900-366X$$aKneussel, Matthias$$b10 000279358 7001_ $$00000-0001-5833-9996$$aBalastik, Martin$$b11 000279358 7001_ $$00000-0001-7053-2000$$aJanke, Carsten$$b12 000279358 7001_ $$0P:(DE-2719)2810727$$aMisgeld, Thomas$$b13 000279358 7001_ $$0P:(DE-2719)9000978$$aBrill, Monika S$$b14 000279358 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-025-60855-6$$gVol. 16, no. 1, p. 5384$$n1$$p5384$$tNature Communications$$v16$$x2041-1723$$y2025 000279358 8564_ $$uhttps://pub.dzne.de/record/279358/files/DZNE-2025-00735%20SUP.zip 000279358 8564_ $$uhttps://pub.dzne.de/record/279358/files/DZNE-2025-00735.pdf$$yOpenAccess 000279358 8564_ $$uhttps://pub.dzne.de/record/279358/files/DZNE-2025-00735.pdf?subformat=pdfa$$xpdfa$$yOpenAccess 000279358 909CO $$ooai:pub.dzne.de:279358$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire 000279358 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810727$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b13$$kDZNE 000279358 9131_ $$0G:(DE-HGF)POF4-351$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vBrain Function$$x0 000279358 9141_ $$y2025 000279358 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2025-01-02 000279358 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2025-01-02 000279358 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2025-01-02 000279358 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2025-01-02 000279358 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess 000279358 915__ $$0StatID:(DE-HGF)1040$$2StatID$$aDBCoverage$$bZoological Record$$d2025-01-02 000279358 915__ $$0StatID:(DE-HGF)9915$$2StatID$$aIF >= 15$$bNAT COMMUN : 2022$$d2025-01-02 000279358 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bNAT COMMUN : 2022$$d2025-01-02 000279358 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2024-01-30T07:48:07Z 000279358 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2024-01-30T07:48:07Z 000279358 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - 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