title: Distinct Regulation of Transmitter Release at the Drosophila NMJ by Different Isoforms of nemy.
abstract: Synaptic transmission is highly plastic and subject to regulation by a wide variety of neuromodulators and neuropeptides. In the present study, we have examined the role of isoforms of the cytochrome b561 homologue called no extended memory (nemy) in regulation of synaptic strength and plasticity at the neuromuscular junction (NMJ) of third instar larvae in Drosophila. Specifically, we generated two independent excisions of nemy that differentially affect the expression of nemy isoforms. We show that the nemy45 excision, which specifically reduces the expression of the longest splice form of nemy, leads to an increase in stimulus evoked transmitter release and altered synaptic plasticity at the NMJ. Conversely, the nemy26.2 excision, which appears to reduce the expression of all splice forms except the longest splice isoform, shows a reduction in stimulus evoked transmitter release, and enhanced synaptic plasticity. We further show that nemy45 mutants have reduced levels of amidated peptides similar to that observed in peptidyl-glycine hydryoxylating mono-oxygenase (PHM) mutants. In contrast, nemy26.2 mutants show no defects in peptide amidation but rather display a decrease in Tyramine β hydroxylase activity (TβH). Taken together, these results show non-redundant roles for the different nemy isoforms and shed light on the complex regulation of neuromodulators.
authors.affiliation: Program in Developmental and Stem Cell Biology, Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, M5G 0A4, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Knight
authors.affiliation: Program in Developmental and Stem Cell Biology, Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, M5G 0A4, Canada.
authors.forename: Konstantin G
authors.initials: KG
authors.lastname: Iliadi
authors.affiliation: Program in Developmental and Stem Cell Biology, Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, M5G 0A4, Canada.
authors.forename: Natalia
authors.initials: N
authors.lastname: Iliadi
authors.affiliation: Department of Molecular Genetics, The Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, M5S 3E1, Canada.
authors.forename: Ronit
authors.initials: R
authors.lastname: Wilk
authors.affiliation: Department of Molecular Genetics, The Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, M5S 3E1, Canada.
authors.forename: Jack
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Molecular Genetics, The Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, M5S 3E1, Canada.
authors.forename: Henry M
authors.initials: HM
authors.lastname: Krause
authors.affiliation: Program in Molecular Structure and Function, The Hospital for Sick Children, Toronto, M5G 1L7, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Taylor
authors.affiliation: Dept of Molecular Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada; Program in Molecular Structure and Function, The Hospital for Sick Children, Toronto, M5G 1L7, Canada.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Moran
authors.affiliation: Program in Developmental and Stem Cell Biology, Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, M5G 0A4, Canada; Dept of Molecular Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
authors.forename: Gabrielle L
authors.initials: GL
authors.lastname: Boulianne
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D003573:Cytochrome b Group / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D009469:Neuromuscular Junction / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D017729:Presynaptic Terminals / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D003573:Cytochrome b Group; D029721:Drosophila Proteins; D020033:Protein Isoforms; C534227:nemy protein, Drosophila