Ephys data for Park IJMS 2021

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Abstract/Contents

Abstract: Fragile X syndrome (FXS) is an X-chromosome-linked neurodevelopmental disorder with severe intellectual disability caused by inactivation of the fragile X mental retardation 1 (FMR1) gene and subsequent loss of the fragile X mental retardation protein (FMRP). Among the various types of abnormal synaptic function and synaptic plasticity phenotypes reported in FXS animal models, defective synaptic retinoic acid (RA) signaling and subsequent defective homeostatic plasticity have emerged as a major synaptic dysfunction. However, the mechanism underlying the defective synaptic RA signaling in the absence of FMRP is unknown. Here we show that RAR, the RA receptor critically involved in synaptic RA signaling, directly interacts with FMRP. This interaction is enhanced in the presence of RA. Blocking the interaction between FMRP and RAR with a small peptide corresponding to the critical binding site in RAR abolishes RA-induced increases in excitatory synaptic transmission, recapitulating the phenotype seen in the Fmr1 knockout mouse. Taken together, these data suggest that not only are functional FMRP and RAR necessary for RA-dependent homeostatic synaptic plasticity, but that the interaction between these two proteins is essential for proper transcription-independent RA signaling. Our results may provide further mechanistic understanding into FXS synaptic pathophysiology.

DOI	https://doi.org/10.25740/qk835gk4326
Location	https://purl.stanford.edu/qk835gk4326

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License: This work is licensed under a Creative Commons Attribution Non Commercial No Derivatives 4.0 International license (CC BY-NC-ND).

Preferred citation: Chen, L., Arendt, K., and Park, E. (2023). Ephys data for Park IJMS 2021. Stanford Digital Repository. Available at https://purl.stanford.edu/qk835gk4326. https://doi.org/10.25740/qk835gk4326.

Research from the Lu Chen Lab at Stanford

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