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Updated: Jul 16, 2025

Dissecting Cell-Autonomous Function of Fragile X Mental Retardation Protein in an Auditory Circuit by In Ovo Electroporation
Published on: July 6, 2022
FMRP Long-Range Transport and Degradation Are Mediated by Dynlrb1 in Sensory Neurons
Sara Emad El-Agamy1, Laurent Guillaud1, Keiko Kono2
1Molecular Neuroscience Unit, Okinawa Institute of Science and Technology Graduate University, Kunigami-gun, Okinawa, Japan.
Abstract:
The fragile X messenger ribonucleoprotein 1 (FMRP) is a multifunctional RNA-binding protein 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 dynein light chain 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 granule accumulation and repressed the translation of microtubule-associated protein 1b, one of its primary mRNA targets. Our findings suggest that Dynlrb1 regulates FMRP function through the control of its transport and targeted degradation.
Insights
Dynein light chain roadblock 1 (Dynlrb1) regulates fragile X mental retardation protein (FMRP) transport in sensory axons. Dynlrb1 controls FMRP function, impacting mRNA translation and neuronal survival in neurological disorders.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Fragile X mental retardation protein (FMRP) is crucial for neuronal development and function.
- FMRP regulates mRNA localization and translation via phase-separated condensates trafficked in axons.
- Axonal transport of FMRP is vital for neuronal survival and linked to neurological diseases.
Purpose of the Study:
- To investigate the role of dynein light chain roadblock 1 (Dynlrb1) in FMRP axonal transport and function.
- To elucidate the mechanism of FMRP retrograde axonal trafficking.
- To understand how Dynlrb1 regulates FMRP-mediated translation.
Main Methods:
- Studied FMRP association with endolysosomal organelles in sensory axons.
- Investigated Dynlrb1-dependent dynein-mediated FMRP retrograde transport.
- Utilized Dynlrb1 silencing to assess effects on FMRP granules and mRNA translation.
Main Results:
- FMRP associates with endolysosomal organelles and undergoes Dynlrb1-dependent retrograde transport in axons.
- Dynlrb1 silencing leads to FMRP granule accumulation.
- Repressed translation of microtubule-associated protein 1b (MAP1B) mRNA was observed upon Dynlrb1 silencing.
Conclusions:
- Dynein light chain roadblock 1 (Dynlrb1) is a critical regulator of FMRP function.
- Dynlrb1 controls FMRP transport and targeted degradation, influencing localized mRNA translation.
- Findings provide insights into FMRP regulation and its implications for neurological disorders.
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