<h3>Abstract</h3> Memory and learning involve activity-driven expression of proteins and cytoskeletal reorganisation at new synapses, often requiring post-transcriptional regulation 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 not yet known. Here, we show that the local translation of <i>msp300</i> is promoted during activity-dependent plasticity by the conserved RNA binding protein Syncrip/hnRNP Q, which binds to <i>msp300</i> transcripts and is essential for plasticity. Single molecule imaging shows that Syncrip is associated <i>in vivo</i> with <i>msp300</i> mRNA in ribosome-rich particles. Elevated neural activity alters the dynamics of Syncrip RNP granules at the synapse, suggesting a change in particle composition or binding that facilitates translation. These results introduce Syncrip as an important early-acting activity-dependent translational regulator of a plasticity gene that is strongly associated with human ataxias. <h3>Syncrip regulates synaptic plasticity via <i>msp300</i></h3> Titlow et al. find that Syncrip (hnRNPQ RNA binding protein) acts directly on <i>msp300</i> to modulate activity-dependent synaptic plasticity. <i>In vivo</i> biophysical experiments reveal activity-dependent changes in RNP complex sizes compatible with an increase in translation at the synapse.
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Jun 4, 1870
Open Access
