Syncrip/hnRNPQ is required for activity-induced Msp300/Nesprin1 expression and new synapse formation

Memory and learning involve activity-driven expression of proteins and cytoskeletal reorganisation at new synapses, requiring post-transcriptional regulation of localized mRNA a long distance from corresponding nuclei. A key factor expressed early in synapse formation is Msp300/Nesprin-1, which organises actin filaments around the new synapse. How Msp300 expression is regulated during synaptic plasticity is poorly understood. Here, we show that activity-dependent accumulation of Msp300 in the post-synaptic compartment of the Drosophila larval neuromuscular junction is regulated by the conserved RNA binding protein Syncrip/hnRN P Q. Syncrip (Syp) binds to msp300 transcripts and is essential for plasticity. Single molecule imaging shows that msp300 is associated with Syp in vivo and forms ribosome-rich granules that contain the translation factor eIF4E. Elevated neural activity alters the dynamics of Syp and the number of msp300:Syp:eIF4E RNP granules at the synapse, suggesting that these particles facilitate translation. These results introduce Syp as an important early-acting activity-dependent regulator of a plasticity gene that is strongly associated with human ataxias