title: Structural organization and function of mouse photoreceptor ribbon synapses involve the immunoglobulin protein synaptic cell adhesion molecule 1.
abstract: Adhesive interactions in the retina instruct the developmental specification of inner retinal layers. However, potential roles of adhesion in the development and function of photoreceptor synapses remain incompletely understood. This contrasts with our understanding of synapse development in the CNS, which can be guided by select adhesion molecules such as the Synaptic Cell Adhesion Molecule 1 (SynCAM 1/CADM1/nectin-like 2 protein). This immunoglobulin superfamily protein modulates the development and plasticity of classical excitatory synapses. We show here by immunoelectron microscopy and immunoblotting that SynCAM 1 is expressed on mouse rod photoreceptors and their terminals in the outer nuclear and plexiform layers in a developmentally regulated manner. Expression of SynCAM 1 on rods is low in early postnatal stages (P3-P7) but increases after eye opening (P14). In support of functional roles in the photoreceptors, electroretinogram recordings demonstrate impaired responses to light stimulation in SynCAM 1 knockout (KO) mice. In addition, the structural integrity of synapses in the OPL requires SynCAM 1. Quantitative ultrastructural analysis of SynCAM 1 KO retina measured fewer fully assembled, triadic rod ribbon synapses. Furthermore, rod synapse ribbons are shortened in KO mice, and protein levels of Ribeye, a major structural component of ribbons, are reduced in SynCAM 1 KO retina. Together, our results implicate SynCAM 1 in the synaptic organization of the rod visual pathway and provide evidence for novel roles of synaptic adhesion in the structural and functional integrity of ribbon synapses.
authors: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, 06520-8024.
authors: Adema
authors: A
authors: Ribic
authors: Xinran
authors: X
authors: Liu
authors: Michael C
authors: MC
authors: Crair
authors: Thomas
authors: T
authors: Biederer
mesh_terms: D000429:Alcohol Oxidoreductases; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism; D004596:Electroretinography; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D012160:Retina / Q000166:cytology* / Q000254:growth & development*; D017948:Retinal Rod Photoreceptor Cells / Q000648:ultrastructure*; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
chemical_list: C498598:Cadm1 protein, mouse; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D007136:Immunoglobulins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D018094:Receptors, Metabotropic Glutamate; C493465:Slc17a7 protein, mouse; D050598:Vesicular Glutamate Transport Protein 1; C113897:metabotropic glutamate receptor 6; D000429:Alcohol Oxidoreductases; C111341:Ctbp2 protein, mouse
keywords: CADM; SynCAM; electroretinography; nectin-like protein; retina; ribbon synapse; rod
references: Nature. 1962 Nov 10;196:547-50
references: 14016006
references: Vis Neurosci. 2006 Jan-Feb;23(1):11-24
references: 16597347
references: Nature. 1985 Aug 15-21;316(6029):630-3
references: 2412124
references: J Comp Neurol. 2008 Sep 1;510(1):47-67
references: 18615557
references: Nature. 2010 Nov 11;468(7321):223-31
references: 21068831
references: J Comp Neurol. 2011 Apr 1;519(5):972-88
references: 21280047
references: J Neurosci. 2007 Nov 14;27(46):12516-30
references: 18003830
references: Science. 2002 Aug 30;297(5586):1525-31
references: 12202822
references: Prog Retin Eye Res. 2008 Jan;27(1):1-44
references: 18042420
references: J Neurosci. 2006 Jul 5;26(27):7201-11
references: 16822977
references: Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):3053-8
references: 21282647
references: J Comp Neurol. 1979 Sep 15;187(2):359-72
references: 489784
references: Anat Rec. 1991 Dec;231(4):482-97
references: 1793176
references: Neuron. 2003 Mar 6;37(5):775-86
references: 12628168
references: J Microsc. 1984 May;134(Pt 2):127-36
references: 6737468
references: Klin Monbl Augenheilkd. 1999 May;214(5):288-90
references: 10420369
references: Brain Res. 1998 Dec 14;814(1-2):55-70
references: 9838044
references: Doc Ophthalmol. 2003 Jul;107(1):13-36
references: 12906119
references: Nature. 1962 Mar 10;193:958 passim
references: 13873685
references: J Neurosci. 2011 Nov 2;31(44):16033-44
references: 22049445
references: J Neurosci. 2012 Jun 6;32(23):8040-52
references: 22674279
references: Nat Rev Neurosci. 2009 Jul;10(7):495-506
references: 19491906
references: Nat Neurosci. 2008 Aug;11(8):923-31
references: 18641643
references: Nat Commun. 2011 Nov 08;2:532
references: 22068599
references: Science. 2001 May 11;292(5519):1178-80
references: 11349152
references: J Neurosci. 2009 Jun 24;29(25):8039-50
references: 19553444
references: Hum Mol Genet. 2005 Oct 15;14(20):3035-46
references: 16155113
references: Eur J Neurosci. 2008 Dec;28(11):2221-30
references: 19019198
references: Invest Ophthalmol Vis Sci. 2010 Nov;51(11):6051-8
references: 20554612
references: J Neurosci. 2012 Oct 10;32(41):14402-14
references: 23055510
references: PLoS Biol. 2011 Apr;9(4):e1001041
references: 21483721
references: Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7568-73
references: 20368431
references: Development. 2008 Dec;135(24):4141-51
references: 19029044
references: J Comp Neurol. 2013 Apr 1;521(5):1119-35
references: 22965528
references: Neuroscience. 2011 Feb 3;174:37-49
references: 21075174
references: Doc Ophthalmol. 1998-1999;97(1):23-31
references: 10710239
references: J Comp Neurol. 1979 Nov 15;188(2):245-62
references: 500858
references: EMBO J. 2002 Apr 2;21(7):1545-54
references: 11927539
references: Vis Neurosci. 2004 Jan-Feb;21(1):23-37
references: 15137579
references: Hum Mol Genet. 2007 May 1;16(9):1017-29
references: 17341488
references: J Neurosci. 2004 Nov 3;24(44):9752-9
references: 15525760
references: J Comp Neurol. 2008 Feb 10;506(5):822-37
references: 18076030
references: J Comp Neurol. 1974 Jul 1;156(1):95-106
references: 4836657
references: Curr Opin Neurobiol. 2009 Aug;19(4):389-94
references: 19660931
references: Annu Rev Neurosci. 2007;30:451-74
references: 17600523
references: J Neurosci. 2012 May 16;32(20):6859-68
references: 22593055
references: J Comp Neurol. 2010 Jun 15;518(12):2365-81
references: 20437533
references: Prog Retin Eye Res. 2005 Nov;24(6):682-720
references: 16027025
references: Brain Res Dev Brain Res. 2003 Oct 10;145(1):93-105
references: 14519497
references: J Comp Neurol. 2003 Oct 27;465(4):480-98
references: 12975811
references: Mol Cell Biol. 2006 Jan;26(2):718-26
references: 16382161
references: J Comp Neurol. 2000 Aug 14;424(1):1-23
references: 10888735
references: J Neurosci. 1993 Nov;13(11):4949-60
references: 8229207
references: Cell Tissue Res. 2006 Nov;326(2):339-46
references: 16775698
references: Nature. 2008 Jan 24;451(7177):465-9
references: 18216854
references: Neuron. 2010 Dec 9;68(5):894-906
references: 21145003
references: J Neurosci. 1996 Jan 15;16(2):563-71
references: 8551340
references: Am J Pathol. 2007 Dec;171(6):1800-10
references: 18055550
references: J Neurophysiol. 2009 Sep;102(3):1945-55
references: 19587322
references: Eur J Cell Biol. 2010 Jun;89(6):468-75
references: 20188438
references: J Neurosci. 2012 Aug 29;32(35):12192-203
references: 22933801
references: J Comp Neurol. 2010 Dec 15;518(24):4938-62
references: 21031560
references: Doc Ophthalmol. 1998-1999;95(3-4):187-215
references: 10532405
references: Nature. 2003 Jun 26;423(6943):939-48
references: 12827191
references: J Biol Chem. 2011 Jul 22;286(29):25835-47
references: 21602278
references: Brain Res Dev Brain Res. 2005 Feb 8;154(2):199-209
references: 15707673
references: J Comp Neurol. 1974 Jul 1;156(1):81-93
references: 4836656
references: Invest Ophthalmol Vis Sci. 2005 Oct;46(10):3836-44
references: 16186371
references: J Neurosci. 1997 Jun 1;17(11):4236-42
references: 9151740
references: J Cell Biol. 2012 Dec 10;199(6):985-1001
references: 23209303
references: J Neurosci. 2002 Jul 1;22(13):5492-504
references: 12097501
references: Doc Ophthalmol. 2007 Nov;115(3):127-36
references: 17636411
references: Neuroscientist. 2009 Dec;15(6):611-24
references: 19700740
references: Invest Ophthalmol Vis Sci. 2007 Jun;48(6):2837-44
references: 17525220
references: J Comp Neurol. 2007 Jan 10;500(2):286-98
references: 17111373
references: J Physiol. 2013 Jul 1;591(13):3309-24
references: 23613534
references: Semin Cell Dev Biol. 2011 Apr;22(2):171-7
references: 20934527
references: Histol Histopathol. 2003 Oct;18(4):1321-9
references: 12973698
references: Proc Natl Acad Sci U S A. 2007 May 22;104(21):8857-62
references: 17496142
references: Neuron. 2004 Sep 16;43(6):779-93
references: 15363390
references: Neuron. 2009 Nov 25;64(4):484-97
references: 19945391
references: J Neurosci. 2003 Jan 15;23(2):518-29
references: 12533612
references: J Biol Chem. 2005 Mar 11;280(10):8694-704
references: 15634683
references: Neuron. 2000 Dec;28(3):857-72
references: 11163272
references: Nat Neurosci. 2011 Jul 24;14(9):1135-41
references: 21785435
references: J Gen Physiol. 1975 Feb;65(2):119-34
references: 1117278
references: Cold Spring Harb Symp Quant Biol. 1965;30:457-82
references: 4956619
references: Dev Dyn. 2008 Jan;237(1):233-46
references: 18095341
references: J Neurosci. 1998 Dec 1;18(23):10136-49
references: 9822767
references: J Cell Sci. 2009 May 1;122(Pt 9):1352-61
references: 19386896
references: J Neurosci. 2013 Jul 17;33(29):11949-59
references: 23864682
references: EMBO J. 2011 Sep 16;30(23):4728-38
references: 21926970
references: Nat Neurosci. 2004 Oct;7(10):1079-87
references: 15452577
references: Invest Ophthalmol Vis Sci. 2012 Nov 27;53(12):7833-46
references: 23074204
references: Hum Mol Genet. 1997 Dec;6(13):2195-203
references: 9361023
references: Doc Ophthalmol. 2011 Jun;122(3):149-56
references: 21465307
references: Cold Spring Harb Perspect Biol. 2012 Apr 01;4(4):a005694
references: 22278667
references: Trends Neurosci. 2005 Jan;28(1):20-9
references: 15626493
references: J Comp Neurol. 2009 Feb 20;512(6):814-24
references: 19067356