title: Drosophila dscam proteins regulate postsynaptic specificity at multiple-contact synapses.
abstract: In both vertebrate and invertebrate visual systems, neurons form multiple-contact synapses at which a single presynaptic site releases neurotransmitter upon a discrete combination of different postsynaptic cells. Recognition mechanisms underlying the assembly of such synapses are not known. In Drosophila, photoreceptor terminals form tetrad synapses that incorporate an invariable pair of postsynaptic elements, one each from lamina interneuron L1 and L2, and two elements from other cells. Here, we demonstrate that Drosophila Dscam1 and Dscam2, genes encoding homophilic repulsive proteins, act redundantly to ensure the invariable combination of L1 and L2 postsynaptic elements at all tetrads. We demonstrate that this strict pairing is lost in Dscam1;Dscam2 double mutants. Thus, removing these two repulsive proteins allows elements from the same cell to incorporate into the same postsynaptic tetrad, altering the specificity of photoreceptor transmission. We propose that Dscams regulate synaptic specificity by excluding inappropriate partners at multiple-contact synapses.
authors.affiliation: Howard Hughes Medical Institute, Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: S Sean
authors.initials: SS
authors.lastname: Millard
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Lu
authors.forename: S Lawrence
authors.initials: SL
authors.lastname: Zipursky
authors.forename: Ian A
authors.initials: IA
authors.lastname: Meinertzhagen
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015815:Cell Adhesion Molecules / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009154:Mutation / Q000235:genetics; D019006:Neural Cell Adhesion Molecules; D009474:Neurons / Q000145:classification / Q000502:physiology* / Q000648:ultrastructure; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D014795:Visual Pathways / Q000166:cytology* / Q000502:physiology
chemical_list: D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; C491736:Dscam1 protein, Drosophila; C520675:Dscam2 protein, Drosophila; D019006:Neural Cell Adhesion Molecules
references.citation: Neuron. 1999 Mar;22(3):451-61
references.pmid: 10197526
references.citation: Cell. 2000 Jun 9;101(6):671-84
references.pmid: 10892653
references.citation: Cell. 2008 Jun 27;133(7):1241-54
references.pmid: 18585357
references.citation: Semin Cell Dev Biol. 2006 Feb;17(1):20-30
references.pmid: 16384719
references.citation: J Microsc. 2005 Apr;218(Pt 1):52-61
references.pmid: 15817063
references.citation: J Neurosci. 1983 Nov;3(11):2336-49
references.pmid: 6631484
references.citation: Neuron. 2007 May 3;54(3):403-16
references.pmid: 17481394
references.citation: Cell. 2007 Sep 21;130(6):1134-45
references.pmid: 17889655
references.citation: Neuron. 2009 Feb 26;61(4):527-40
references.pmid: 19249274
references.citation: Nature. 2007 Sep 13;449(7159):223-7
references.pmid: 17851526
references.citation: J Neurosci. 1991 Jan;11(1):1-22
references.pmid: 1986064
references.citation: Neuron. 2008 Oct 23;60(2):328-42
references.pmid: 18957224
references.citation: Neuron. 2002 Feb 14;33(4):559-71
references.pmid: 11856530
references.citation: Prog Brain Res. 2001;131:53-69
references.pmid: 11420968
references.citation: Neuron. 2004 Sep 2;43(5):673-86
references.pmid: 15339649
references.citation: J Comp Neurol. 2008 Aug 10;509(5):493-513
references.pmid: 18537121
references.citation: Neuroscience. 2005;134(3):783-90
references.pmid: 16009499
references.citation: J Comp Neurol. 1991 Mar 8;305(2):232-63
references.pmid: 1902848
references.citation: Neuron. 2007 Oct 4;56(1):155-70
references.pmid: 17920022
references.citation: J Neurosci Methods. 1996 Oct 21;69(1):59-73
references.pmid: 8912936
references.citation: Nature. 2008 Jan 24;451(7177):470-4
references.pmid: 18216855
references.citation: Nat Genet. 2004 Mar;36(3):240-6
references.pmid: 14758360
references.citation: Proc R Soc Lond B Biol Sci. 1966 Nov 15;166(1002):80-111
references.pmid: 4382694
references.citation: Cell. 2004 Sep 3;118(5):619-33
references.pmid: 15339666
references.citation: Nature. 2007 Jun 7;447(7145):720-4
references.pmid: 17554308
references.citation: Proc Natl Acad Sci U S A. 1986 Oct;83(20):7961-5
references.pmid: 3464012
references.citation: Neuron. 2002 Aug 29;35(5):827-41
references.pmid: 12372279
references.citation: Philos Trans R Soc Lond B Biol Sci. 1986 Nov 12;314(1165):1-340
references.pmid: 22462104
references.citation: Nature. 2008 Jan 24;451(7177):465-9
references.pmid: 18216854
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2951-6
references.pmid: 19196994
references.citation: Neuron. 2007 May 3;54(3):417-27
references.pmid: 17481395
references.citation: Development. 2008 Dec;135(23):3839-48
references.pmid: 18948420
references.citation: Neuron. 2001 May;30(2):437-50
references.pmid: 11395005
references.citation: J Comp Physiol A. 1987 Aug;161(2):201-13
references.pmid: 2442380
references.citation: Neuron. 2009 Nov 25;64(4):484-97
references.pmid: 19945391
references.citation: Cell. 2007 May 4;129(3):593-604
references.pmid: 17482551