FMRP long-range transport and degradation are mediated by Dynlrb1 in sensory neurons

Mol Cell Proteomics. 2023 Sep 20:100653. doi: 10.1016/j.mcpro.2023.100653. Online ahead of print.ABSTRACTThe fragile X messenger ribonucleoprotein 1 (FMRP) is a multifunctional RNA binding protein (RBP) implicated in human neurodevelopmental and neurodegenerative disorders. FMRP mediates the localization and activity-dependent translation of its associated mRNAs through the formation of phase separated condensates that are trafficked by microtubule-based motors in axons. Axonal transport and localized mRNA translation are critical processes for long-term neuronal survival and are closely linked to the pathogenesis of neurological diseases. FMRP dynein-mediated axonal trafficking is still largely unexplored, but likely to constitute a key process underlying FMRP spatiotemporal translational regulation. Here, we show that roadblock 1 (Dynlrb1), a subunit of the dynein complex, is a critical regulator of FMRP function. In sensory axons, FMRP associates with endolysosomal organelles, likely through annexin A11, and is retrogradely trafficked by the dynein complex in a Dynlrb1-dependent manner. Moreover, Dynlrb1 silencing induced FMRP granules accumulation and repressed the translation of Map1b, one of its primary mRNA targets. Our findings suggest that Dynlrb1 regulates FMRP function through the control of its transport and targeted degradation.PMID:37739344 | DOI:10.1016/j.mcpro.2023.100653
Source: Molecular and Cellular Proteomics : MCP - Category: Molecular Biology Authors: Source Type: research