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
• Názvy látek
• kyselina polyglutamová * MeSH
• peptidsynthasy MeSH
• spastin MeSH
• tubulin polyglutamylase MeSH Prohlížeč
• tubulin MeSH

Microtubule doublets (MTDs) comprise an incomplete microtubule (B-tubule) attached to the side of a complete cylindrical microtubule. These compound microtubules are conserved in cilia across the tree of life; however, the mechanisms by which MTDs form and are maintained in vivo remain poorly understood. Here, we identify microtubule-associated protein 9 (MAP9) as an MTD-associated protein. We demonstrate that C. elegans MAPH-9, a MAP9 homolog, is present during MTD assembly and localizes exclusively to MTDs, a preference that is in part mediated by tubulin polyglutamylation. We find that loss of MAPH-9 causes ultrastructural MTD defects, including shortened and/or squashed B-tubules with reduced numbers of protofilaments, dysregulated axonemal motor velocity, and perturbed cilia function. Because we find that the mammalian ortholog MAP9 localizes to axonemes in cultured mammalian cells and mouse tissues, we propose that MAP9/MAPH-9 plays a conserved role in regulating ciliary motors and supporting the structure of axonemal MTDs.

• Klíčová slova
• C. elegans, MAP9, axoneme, cilia, dynein, kinesin, microtubule, microtubule doublet, microtubule-associated protein, polyglutamylation,
• MeSH
• axonema * metabolismus   ultrastruktura   MeSH
• Caenorhabditis elegans * metabolismus   MeSH
• cilie metabolismus   MeSH
• mikrotubuly metabolismus   MeSH
• myši MeSH
• pohyb MeSH
• savci MeSH
• tubulin metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• Map9 protein, mouse MeSH Prohlížeč
• tubulin MeSH