Related Experiment Video
Updated: Jun 10, 2026
Dissecting Cell-Autonomous Function of Fragile X Mental Retardation Protein in an Auditory Circuit by In Ovo Electroporation
Published on: July 6, 2022
Bicaudal-D regulates fragile X mental retardation protein levels, motility, and function during neuronal
Ambra Bianco1, Martin Dienstbier, Hannah K Salter
1Cell Biology Division, MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.
Abstract:
The expression of the RNA-binding factor Fragile X mental retardation protein (FMRP) is disrupted in the most common inherited form of cognitive deficiency in humans. FMRP controls neuronal morphogenesis by mediating the translational regulation and localization of a large number of mRNA targets, and these functions are closely associated with transport of FMRP complexes within neurites by microtubule-based motors. However, the mechanisms that link FMRP to motors and regulate its transport are poorly understood. Here we show that FMRP is complexed with Bicaudal-D (BicD) through a domain in the latter protein that mediates linkage of cargoes with the minus-end-directed motor dynein. We demonstrate in Drosophila that the motility and, surprisingly, levels of FMRP protein are dramatically reduced in BicD mutant neurons, leading to a paucity of FMRP within processes. We also provide functional evidence that BicD and FMRP cooperate to control dendritic morphogenesis in the larval nervous system. Our findings open new perspectives for understanding localized mRNA functions in neurons.
Insights
Fragile X mental retardation protein (FMRP) transport in neurons is mediated by Bicaudal-D (BicD). BicD deficiency reduces FMRP levels and impacts neuronal development, revealing a new mechanism for mRNA regulation.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Fragile X mental retardation protein (FMRP) is crucial for neuronal development and is implicated in cognitive deficiencies.
- FMRP's role in neuronal morphogenesis involves mRNA regulation and transport via microtubule-based motors, but the linking mechanisms are unclear.
Purpose of the Study:
- To elucidate the mechanisms linking FMRP to motor proteins for transport within neurons.
- To investigate the role of Bicaudal-D (BicD) in FMRP transport and neuronal development.
Main Methods:
- Investigated the interaction between FMRP and Bicaudal-D (BicD) using protein complex analysis.
- Utilized Drosophila melanogaster as a model system to study FMRP and BicD function in neurons.
- Assessed FMRP protein levels, motility, and localization in BicD mutant neurons.
Main Results:
- FMRP forms a complex with Bicaudal-D (BicD), specifically through a domain that links cargoes to the dynein motor.
- In Drosophila, BicD deficiency significantly reduces FMRP protein levels and its transport within neuronal processes.
- BicD and FMRP were found to cooperate in controlling dendritic morphogenesis in the larval nervous system.
Conclusions:
- Bicaudal-D (BicD) is essential for the transport and maintenance of Fragile X mental retardation protein (FMRP) levels in neurons.
- The findings reveal a novel mechanism connecting motor proteins to mRNA regulation, impacting neuronal structure and function.
- This study provides new insights into localized mRNA functions in neurons and their implications for cognitive development.
