Nucleus to Synapse Nesprin1 Railroad Tracks Direct Synapse Maturation through RNA Localization

• Nesprin1 forms actin-based railroad tracks from nucleus to synaptic boutons
• Nesprin1 is required for postsynaptic RNA localization and new bouton formation
• Nesprin1 function depends on unconventional Myosin, Myo1D
• We provide a mechanism for directed postsynaptic maturation via RNA localization

SummaryAn important mechanism underlying synapse development and plasticity is the localization of mRNAs that travel from the nucleus to synaptic sites. Here we demonstrate that the giant nuclear-associated Nesprin1 (dNesp1) forms striated F-actin-based filaments, which we dubbed “railroad tracks,” that span from muscle nuclei to postsynaptic sites at the neuromuscular junction in Drosophila. These railroad tracks specifically wrap around immature boutons formed during development and in response to electrical activity. In the absence of dNesp1, mRNAs normally localized at postsynaptic sites are lacking and synaptic maturation is inhibited. This dNesp1 function does not depend on direct association of dNesp1 isoforms with the nuclear envelope. We also show that dNesp1 functions with an unconventional myosin, Myo1D, and that both dNesp1 and Myo1D are mutually required for their localization to immature boutons. These studies unravel a novel pathway directing the transport of mRNAs from the nucleus to postsynaptic sites during synaptic maturation.Video Abstract To view the video inline, enable JavaScript on your browser. However, you can download and view the video by clicking on the icon belowHelp with MP4 filesOptionsDownload video (35827 K)