A rapid and dynamic role for FMRP in the plasticity of adult neurons

bioRxiv [Preprint]. 2023 Sep 3:2023.09.01.555985. doi: 10.1101/2023.09.01.555985.

Abstract

Fragile X syndrome (FXS) is a neuro-developmental disorder caused by silencing Fmr1, which encodes the RNA-binding protein FMRP. Although Fmr1 is expressed in adult neurons, it has been challenging to separate acute from chronic effects of loss of Fmr1 in models of FXS. We have used the precision of Drosophila genetics to test if Fmr1 acutely affects adult neuronal plasticity in vivo, focusing on the s-LNv circadian pacemaker neurons that show 24 hour rhythms in structural plasticity. We found that over-expressing Fmr1 for only 4 hours blocks the activity-dependent expansion of s-LNv projections without altering the circadian clock or activity-regulated gene expression. Conversely, acutely reducing Fmr1 expression prevented s-LNv projections from retracting. One FMRP target that we identified in s-LNvs is sif, which encodes a Rac1 GEF. Our data indicate that FMRP normally reduces sif mRNA translation at dusk to reduce Rac1 activity. Overall, our data reveal a previously unappreciated rapid and direct role for FMRP in acutely regulating neuronal plasticity in adult neurons, and underscore the importance of RNA-binding proteins in this process.

Publication types

  • Preprint