title: Netrin and Frazzled regulate presynaptic gap junctions at a Drosophila giant synapse.
abstract: Netrin and its receptor, Frazzled, dictate the strength of synaptic connections in the giant fiber system (GFS) of Drosophila melanogaster by regulating gap junction localization in the presynaptic terminal. In Netrin mutant animals, the synaptic coupling between a giant interneuron and the "jump" motor neuron was weakened and dye coupling between these two neurons was severely compromised or absent. In cases in which Netrin mutants displayed apparently normal synaptic anatomy, half of the specimens exhibited physiologically defective synapses and dye coupling between the giant fiber (GF) and the motor neuron was reduced or eliminated, suggesting that gap junctions were disrupted in the Netrin mutants. When we examined the gap junctions with antibodies to Shaking-B (ShakB) Innexin, they were significantly decreased or absent in the presynaptic terminal of the mutant GF. Frazzled loss of function mutants exhibited similar defects in synaptic transmission, dye coupling, and gap junction localization. These data are the first to show that Netrin and Frazzled regulate the placement of gap junctions presynaptically at a synapse.
authors.affiliation: Department of Biological Sciences, Florida Atlantic University, Boca Raton, Florida 33431.
authors.forename: Brian O
authors.initials: BO
authors.lastname: Orr
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Borgen
authors.forename: Phyllis M
authors.initials: PM
authors.lastname: Caruccio
authors.forename: Rodney K
authors.initials: RK
authors.lastname: Murphey
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D003712:Dendrites / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D008954:Models, Biological; D009046:Motor Neurons / Q000502:physiology; D009154:Mutation / Q000235:genetics; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009415:Nerve Net / Q000502:physiology; D000075386:Netrin Receptors; D000075388:Netrin-1; D009469:Neuromuscular Junction / Q000166:cytology* / Q000502:physiology; D017729:Presynaptic Terminals / Q000502:physiology*; D011679:Pupa; D011930:Reaction Time / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D009414:Nerve Growth Factors; C583437:NetB protein, Drosophila; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; C000617310:fra protein, Drosophila; D000075388:Netrin-1
keywords: Drosophila; Frazzled; Netrin; electrophysiology; gap junctions; giant fiber system
references.citation: Neuron. 1990 Jan;4(1):61-85
references.pmid: 2310575
references.citation: Science. 2007 Oct 5;318(5847):103-6
references.pmid: 17916735
references.citation: J Neurosci. 2008 Aug 20;28(34):8615-23
references.pmid: 18716220
references.citation: Cold Spring Harb Protoc. 2010 Jul 01;2010(7):pdb.prot5453
references.pmid: 20647357
references.citation: J Cell Biol. 2012 Apr 2;197(1):75-88
references.pmid: 22451697
references.citation: J Comp Neurol. 1998 Aug 10;397(4):519-31
references.pmid: 9699913
references.citation: J Neurosci. 2006 Jan 4;26(1):265-72
references.pmid: 16399696
references.citation: Dev Biol. 2011 Feb 1;350(1):89-100
references.pmid: 21094637
references.citation: J Comp Neurol. 1999 Feb 22;404(4):449-58
references.pmid: 9987990
references.citation: J Vis Exp. 2011 Jan 14;(47):
references.pmid: 21304452
references.citation: Development. 2007 Dec;134(24):4325-34
references.pmid: 18003737
references.citation: J Neurosci. 1996 Feb 1;16(3):1101-13
references.pmid: 8558239
references.citation: Science. 2009 May 15;324(5929):944-7
references.pmid: 19325078
references.citation: Curr Biol. 2008 Dec 23;18(24):1955-60
references.pmid: 19084406
references.citation: Neuron. 1996 Jan;16(1):35-46
references.pmid: 8562088
references.citation: J Vis Exp. 2011 Jun 04;(52):
references.pmid: 21673644
references.citation: Eur J Neurosci. 2007 Jul;26(2):439-45
references.pmid: 17650116
references.citation: Neuron. 2012 Jul 12;75(1):80-93
references.pmid: 22794263
references.citation: PLoS Biol. 2009 Sep;7(9):e1000199
references.pmid: 19771147
references.citation: Mech Dev. 1997 Feb;62(1):79-91
references.pmid: 9106169
references.citation: Nat Neurosci. 2003 Mar;6(3):223-30
references.pmid: 12592406
references.citation: J Neurobiol. 1996 Jul;30(3):340-8
references.pmid: 8807527
references.citation: PLoS Biol. 2009 Sep;7(9):e1000200
references.pmid: 19771146
references.citation: Neuron. 1996 Aug;17(2):203-15
references.pmid: 8780645
references.citation: J Neurogenet. 2010 Sep;24(3):158-67
references.pmid: 20615087
references.citation: Neuroscience. 2005;136(3):661-80
references.pmid: 16344143
references.citation: Dev Biol. 2012 Jan 15;361(2):232-44
references.pmid: 22061481
references.citation: Development. 2000 Dec;127(23):5203-12
references.pmid: 11060245
references.citation: J Neurophysiol. 1980 Aug;44(2):405-21
references.pmid: 6774064
references.citation: Cell. 1996 Oct 18;87(2):197-204
references.pmid: 8861904
references.citation: Nat Neurosci. 2006 Feb;9(2):188-94
references.pmid: 16429137
references.citation: Cell. 1999 Jun 25;97(7):917-26
references.pmid: 10399919
references.citation: Cell Adh Migr. 2009 Jul-Sep;3(3):268-71
references.pmid: 19377288
references.citation: Dev Biol. 1999 May 15;209(2):381-98
references.pmid: 10328928
references.citation: Nature. 2000 Aug 24;406(6798):886-9
references.pmid: 10972289
references.citation: Cell. 1998 May 15;93(4):581-91
references.pmid: 9604933
references.citation: Development. 1993 Jun;118(2):401-15
references.pmid: 8223268
references.citation: Semin Cell Dev Biol. 2006 Feb;17(1):31-41
references.pmid: 16378740
references.citation: J Neurosci. 2007 Mar 28;27(13):3584-92
references.pmid: 17392474
references.citation: Nat Neurosci. 2012 Mar 18;15(5):731-7
references.pmid: 22426253
references.citation: Mech Dev. 1993 Mar;40(3):141-54
references.pmid: 8494768