RT Journal Article
SR Electronic
T1 Syncrip/hnRNPQ is required for activity-induced Msp300/Nesprin-1 expression and new synapse formation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 585679
DO 10.1101/585679
A1 Josh Titlow
A1 Francesca Robertson
A1 Aino Järvelin
A1 David Ish-Horowicz
A1 Carlas Smith
A1 Enrico Gratton
A1 Ilan Davis
YR 2019
UL http://biorxiv.org/content/early/2019/03/22/585679.abstract
AB 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 msp300 is promoted during activity-dependent plasticity by the conserved RNA binding protein Syncrip/hnRNP Q, which binds to msp300 transcripts and is essential for plasticity. Single molecule imaging shows that Syncrip is associated in vivo with msp300 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.Syncrip regulates synaptic plasticity via msp300 Titlow et al. find that Syncrip (hnRNPQ RNA binding protein) acts directly on msp300 to modulate activity-dependent synaptic plasticity. In vivo biophysical experiments reveal activity-dependent changes in RNP complex sizes compatible with an increase in translation at the synapse.