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Publication : Local protein synthesis at neuromuscular synapses is required for motor functions.

First Author  Tu WY Year  2024
Journal  Cell Rep Volume  43
Issue  9 Pages  114661
PubMed ID  39178112 Mgi Jnum  J:354621
Mgi Id  MGI:7736107 Doi  10.1016/j.celrep.2024.114661
Citation  Tu WY, et al. (2024) Local protein synthesis at neuromuscular synapses is required for motor functions. Cell Rep 43(9):114661
abstractText  Motor neurons are highly polarized, and their axons extend over great distances to form connections with myofibers via neuromuscular junctions (NMJs). Local translation at the NMJs in vivo has not been identified. Here, we utilized motor neuron-labeled RiboTag mice and the TRAP (translating ribosome affinity purification) technique to spatiotemporally profile the translatome at NMJs. We found that mRNAs associated with glucose catabolism, synaptic connection, and protein homeostasis are enriched at presynapses. Local translation at the synapse shifts from the assembly of cytoskeletal components during early developmental stages to energy production in adulthood. The mRNA of neuronal Agrin (Agrn), the key molecule for NMJ assembly, is present at motor axon terminals and locally translated. Disrupting the axonal location of Agrn mRNA causes impairment of synaptic transmission and motor functions in adult mice. Our findings indicate that spatiotemporal regulation of mRNA local translation at NMJs plays critical roles in synaptic transmission and motor functions in vivo.
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