Abstract
Motoneurons critically depend on precise spatial and temporal control of translation for axon growth and the establishment and maintenance of neuromuscular connections. While defects in local translation have been implicated in the pathogenesis of motoneuron disorders, little is known about the mechanisms regulating axonal protein synthesis. Here, we report that motoneurons derived from Hnrnpr knockout mice show reduced axon growth accompanied by lowered synthesis of cytoskeletal and synaptic components in axons. Mutant mice display denervated neuromuscular junctions and impaired motor behavior. In axons, hnRNP R is a component of translation initiation complexes and, through interaction with O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt), modulates O-GlcNAcylation of eIF4G. Restoring axonal O-GlcNAc levels rescued local protein synthesis and axon growth defects of hnRNP R knockout motoneurons. Together, these findings demonstrate a function of hnRNP R in controlling the local production of key factors required for axon growth and formation of neuromuscular innervations.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 7430 |
| Tidsskrift | Nature Communications |
| Vol/bind | 15 |
| Udgave nummer | 1 |
| Antal sider | 20 |
| ISSN | 2041-1723 |
| DOI | |
| Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:The authors thank the Core Unit SysMed at the University of Wuerzburg for excellent technical support, RNA-seq data generation, and analysis. The Core Unit SysMed is supported by the IZKF at the University of Wuerzburg (project Z-6). We thank Flinders University for providing the p75NTR antibody. This work was supported by the Deutsche Forschungsgemeinschaft [BR4910/1-2 (SPP1738) and BR4910/2\u20132 (SPP1935) to M.B., SE697/4-2 (SPP1738) and SE697/5\u20132 (SPP1935) to M.S., Fi573/15-2 (SPP1935) and Fi573/20-1 to U.F.] and a Grant from the Schilling Stiftung im Stifterverband f\u00FCr die Deutsche Wissenschaft to M.S.
Publisher Copyright:
© The Author(s) 2024.