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Polyglutamylation of microtubules drives neuronal remodeling

A. Gavoci, A. Zhiti, M. Rusková, MM. Magiera, M. Wang, KA. Ziegler, TJ. Hausrat, AI. Ugwuja, S. Chakraborty, S. Engelhardt, M. Kneussel, M. Balastik, C. Janke, T. Misgeld, MS. Brill

. 2025 ; 16 (1) : 5384. [pub] 20250625

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25015255

Grantová podpora
390857198 Deutsche Forschungsgemeinschaft (German Research Foundation)
450131873 Deutsche Forschungsgemeinschaft (German Research Foundation)
403584255 Deutsche Forschungsgemeinschaft (German Research Foundation)
523862973 Deutsche Forschungsgemeinschaft (German Research Foundation)
390857198 Deutsche Forschungsgemeinschaft (German Research Foundation)
428663564 Deutsche Forschungsgemeinschaft (German Research Foundation)
408885537 Deutsche Forschungsgemeinschaft (German Research Foundation)
2023 Association France Alzheimer (French Alzheimer's Association)
CNATM Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
ANR-17-CE13-0021 Agence Nationale de la Recherche (French National Research Agency)
ANR-20-CE13-0011 Agence Nationale de la Recherche (French National Research Agency)
FP/2007-2013; 616791 EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))

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.

Citace poskytuje Crossref.org

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