| First Author | Park E | Year | 2021 |
| Journal | Int J Mol Sci | Volume | 22 |
| Issue | 12 | PubMed ID | 34205274 |
| Mgi Jnum | J:308445 | Mgi Id | MGI:6727754 |
| Doi | 10.3390/ijms22126579 | Citation | Park E, et al. (2021) FMRP Interacts with RARalpha in Synaptic Retinoic Acid Signaling and Homeostatic Synaptic Plasticity. Int J Mol Sci 22(12) |
| abstractText | The 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 RARalpha, 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 RARalpha with a small peptide corresponding to the critical binding site in RARalpha 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 RARalpha 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. |
