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000279358 1001_ $$00000-0002-9985-6508$$aGavoci, Antoneta$$b0
000279358 245__ $$aPolyglutamylation of microtubules drives neuronal remodeling.
000279358 260__ $$a[London]$$bSpringer Nature$$c2025
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000279358 520__ $$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.
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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
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