title: The Drosophila miR-310 cluster negatively regulates synaptic strength at the neuromuscular junction.
abstract: Emerging data implicate microRNAs (miRNAs) in the regulation of synaptic structure and function, but we know little about their role in the regulation of neurotransmission in presynaptic neurons. Here, we demonstrate that the miR-310-313 cluster is required for normal synaptic transmission at the Drosophila larval neuromuscular junction. Loss of miR-310-313 cluster leads to a significant enhancement of neurotransmitter release, which can be rescued with temporally restricted expression of mir-310-313 in larval presynaptic neurons. Kinesin family member, Khc-73 is a functional target for miR-310-313 as its expression is increased in mir-310-313 mutants and reducing it restores normal synaptic function. Cluster mutants show an increase in the active zone protein Bruchpilot accompanied by an increase in electron dense T bars. Finally, we show that repression of Khc-73 by miR-310-313 cluster influences the establishment of normal synaptic homeostasis. Our findings establish a role for miRNAs in the regulation of neurotransmitter release.
authors.affiliation: Department of Physiology, McGill University, Montréal, QC H3G 1Y6, Canada.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Tsurudome
authors.forename: Karen
authors.initials: K
authors.lastname: Tsang
authors.forename: Edward H
authors.initials: EH
authors.lastname: Liao
authors.forename: Robin
authors.initials: R
authors.lastname: Ball
authors.forename: Jay
authors.initials: J
authors.lastname: Penney
authors.forename: Jr-Shiuan
authors.initials: JS
authors.lastname: Yang
authors.forename: Fatima
authors.initials: F
authors.lastname: Elazzouzi
authors.forename: Tao
authors.initials: T
authors.lastname: He
authors.forename: Athar
authors.initials: A
authors.lastname: Chishti
authors.forename: Greg
authors.initials: G
authors.lastname: Lnenicka
authors.forename: Eric C
authors.initials: EC
authors.lastname: Lai
authors.forename: A Pejmun
authors.initials: AP
authors.lastname: Haghighi
mesh_terms: D000818:Animals; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism; D007814:Larva / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D009046:Motor Neurons / Q000378:metabolism; D005810:Multigene Family / Q000235:genetics; D009469:Neuromuscular Junction / Q000235:genetics* / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics* / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; C104644:Khc-73 protein, Drosophila; D035683:MicroRNAs; D016547:Kinesins