Local protein synthesis at neuromuscular synapses is required for motor functions
Wen-Yo Tu,
Wentao Xu,
Lei Bai,
Jun Liu,
Yi Han,
Benyan Luo,
Bingwei Wang,
Kejing Zhang,
Chengyong Shen
Affiliations
Wen-Yo Tu
Department of Neurobiology of First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310020, China
Wentao Xu
Department of Neurobiology of First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310020, China
Lei Bai
Department of Neurobiology of First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310020, China
Jun Liu
School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
Yi Han
Department of Neurobiology of First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310020, China
Benyan Luo
Department of Neurobiology of First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310020, China
Bingwei Wang
School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
Kejing Zhang
Zhejiang Provincial Key Laboratory of Pancreatic Disease, MOE Joint International Research Laboratory of Pancreatic Diseases, First Affiliated Hospital, Hangzhou 310006, China; Corresponding author
Chengyong Shen
Department of Neurobiology of First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310020, China; MOE Frontier Science Center for Brain Research and Brain-Machine Integration, Zhejiang University, Hangzhou 310058, China; Corresponding author
Summary: 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.
