title: Nucleus to Synapse Nesprin1 Railroad Tracks Direct Synapse Maturation through RNA Localization.
abstract: 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. VIDEO ABSTRACT.
authors.affiliation: Department of Neurobiology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01452, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Packard
authors.affiliation: Department of Neurobiology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01452, USA.
authors.forename: Vahbiz
authors.initials: V
authors.lastname: Jokhi
authors.affiliation: Department of Neurobiology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01452, USA.
authors.forename: Baojin
authors.initials: B
authors.lastname: Ding
authors.affiliation: Department of Neurobiology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01452, USA.
authors.forename: Catalina
authors.initials: C
authors.lastname: Ruiz-Cañada
authors.affiliation: Department of Neurobiology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01452, USA.
authors.forename: James
authors.initials: J
authors.lastname: Ashley
authors.affiliation: Department of Neurobiology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01452, USA. Electronic address: vivian.budnik@umassmed.edu.
authors.forename: Vivian
authors.initials: V
authors.lastname: Budnik
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism*; D038081:Organogenesis / Q000502:physiology; D012313:RNA / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000378:metabolism*
chemical_list: D000199:Actins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; C079806:Msp300 protein, Drosophila; D009124:Muscle Proteins; D012313:RNA