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.

• MeSH
• hipokampus metabolismus   cytologie   MeSH
• kyselina polyglutamová * metabolismus   MeSH
• mikrotubuly * metabolismus   MeSH
• motorické neurony * metabolismus   MeSH
• myši MeSH
• nervosvalové spojení metabolismus   MeSH
• nervový přenos MeSH
• neurony * metabolismus   MeSH
• neuroplasticita * fyziologie   MeSH
• peptidsynthasy metabolismus   genetika   MeSH
• posttranslační úpravy proteinů MeSH
• spastin metabolismus   MeSH
• synapse metabolismus   MeSH
• tubulin metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH