Nucleus to Synapse Nesprin1 Railroad Tracks Direct Synapse Maturation through RNA Localization
Department of Neurobiology; Budnik Lab; Graduate School of Biomedical Sciences, Neuroscience Program
Actins; Animals; Cell Nucleus; Drosophila; Drosophila Proteins; Microfilament Proteins; Muscle Proteins; Neuromuscular Junction; Organogenesis; RNA; Signal Transduction; Synapses
Developmental Neuroscience | Molecular and Cellular Neuroscience
An 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.
DOI of Published Version
Neuron. 2015 May 20;86(4):1015-28. doi: 10.1016/j.neuron.2015.04.006. Epub 2015 May 7. Link to article on publisher's site
Packard M, Jokhi V, Ding B, Ruiz-Canada C, Ashley JA, Budnik V. (2015). Nucleus to Synapse Nesprin1 Railroad Tracks Direct Synapse Maturation through RNA Localization. Neurobiology Publications. https://doi.org/10.1016/j.neuron.2015.04.006. Retrieved from https://escholarship.umassmed.edu/neurobiology_pp/147