title: RGS9 knockout causes a short delay in light responses of ON-bipolar cells.
abstract: RGS9 and R9AP are components of the photoreceptor-specific GTPase activating complex responsible for rapid inactivation of the G protein, transducin, in the course of photoresponse recovery from excitation. The amount of this complex in photoreceptors is strictly dependent on the expression level of R9AP; consequently, the knockouts of either RGS9 or R9AP cause comparable delays in photoresponse recovery. While RGS9 is believed to be present only in rods and cones, R9AP is also expressed in dendritic tips of ON-bipolar cells, which receive synaptic inputs from photoreceptors. Recent studies demonstrated that knockouts of R9AP and its binding partner in ON-bipolar cells, RGS11, cause a small delay in ON-bipolar cell light responses manifested as a delayed onset of electroretinography b-waves. This led the authors to suggest that R9AP and RGS11 participate in regulating the kinetics of light responses in these cells. Here we report the surprising finding that a nearly identical b-wave delay is observed in RGS9 knockout mice. Given the exclusive localization of RGS9 in photoreceptors, this result argues for a presynaptic origin of the b-wave delay in this case and perhaps in the case of the R9AP knockout as well, since R9AP is expressed in both photoreceptors and ON-bipolar cells. We also conducted a detailed analysis of the b-wave rising phase kinetics in both knockout animal types and found that, despite a delayed b-wave onset, the slope of the light response is unaffected or increased, dependent on the light stimulus intensity. This result is inconsistent with a slowdown of response propagation in ON-bipolar cells caused by the R9AP knockout, further arguing against the postsynaptic nature of the delayed b-wave phenotype in RGS9 and R9AP knockout mice.
authors.affiliation: Albert Eye Research Institute, Duke University, Durham, North Carolina, United States of America.
authors.forename: Rolf
authors.initials: R
authors.lastname: Herrmann
authors.forename: Bowa
authors.initials: B
authors.lastname: Lee
authors.forename: Vadim Y
authors.initials: VY
authors.lastname: Arshavsky
mesh_terms: D000818:Animals; D004596:Electroretinography; D008027:Light; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010786:Photoreceptor Cells / Q000378:metabolism / Q000528:radiation effects; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D051245:Retinal Bipolar Cells / Q000378:metabolism* / Q000528:radiation effects
chemical_list: D008565:Membrane Proteins; C508769:R9AP protein, mouse; D020710:RGS Proteins; C485693:Rgs11 protein, mouse; C116925:regulator of g-protein signaling 9
references.citation: Science. 1991 Feb 22;251(4996):915-8
references.pmid: 1672047
references.citation: Invest Ophthalmol Vis Sci. 2010 Feb;51(2):1121-9
references.pmid: 19797214
references.citation: Eur J Neurosci. 2008 May;27(10):2691-700
references.pmid: 18547251
references.citation: J Neurosci. 2009 Jun 17;29(24):7753-65
references.pmid: 19535587
references.citation: J Neurosci. 2002 Mar 15;22(6):2063-73
references.pmid: 11896146
references.citation: J Neurosci. 1999 Apr 15;19(8):2938-44
references.pmid: 10191311
references.citation: Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7553-7
references.pmid: 10377453
references.citation: Nat Biotechnol. 1997 Oct;15(10):965-70
references.pmid: 9335046
references.citation: Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5351-6
references.pmid: 9560279
references.citation: Neuron. 2006 Aug 17;51(4):409-16
references.pmid: 16908407
references.citation: Proc Natl Acad Sci U S A. 2004 Nov 16;101(46):16339-44
references.pmid: 15534226
references.citation: J Biol Chem. 1995 Jul 7;270(27):16147-52
references.pmid: 7608179
references.citation: Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):1947-52
references.pmid: 10051575
references.citation: Nature. 2000 Feb 3;403(6769):557-60
references.pmid: 10676965
references.citation: J Biol Chem. 2002 Jul 5;277(27):24376-81
references.pmid: 12006596
references.citation: Cell. 1995 Mar 10;80(5):757-65
references.pmid: 7889569
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):332-7
references.pmid: 19966281
references.citation: J Biol Chem. 2003 Apr 18;278(16):14550-4
references.pmid: 12560335
references.citation: Mol Cell Neurosci. 2007 Jun;35(2):311-9
references.pmid: 17442586
references.citation: Am J Hum Genet. 2009 Nov;85(5):730-6
references.pmid: 19896109
references.citation: J Biol Chem. 1987 Jan 15;262(2):757-61
references.pmid: 3027067
references.citation: J Neurosci. 2002 Jun 15;22(12):4878-84
references.pmid: 12077185
references.citation: Annu Rev Neurosci. 2001;24:779-805
references.pmid: 11520918
references.citation: J Neurosci. 2003 Nov 12;23(32):10175-81
references.pmid: 14614075
references.citation: Cell Calcium. 2010 Aug-Sep;48(2-3):95-101
references.pmid: 20846719
references.citation: Eur J Neurosci. 2007 Nov;26(10):2899-905
references.pmid: 18001285
references.citation: J Neurosci. 2005 Feb 23;25(8):2157-65
references.pmid: 15728856
references.citation: Neuron. 2003 Jun 19;38(6):941-52
references.pmid: 12818179
references.citation: J Neurosci. 1997 May 1;17(9):3014-23
references.pmid: 9096137
references.citation: J Neurosci. 2010 Mar 3;30(9):3239-53
references.pmid: 20203183
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 22;105(29):9855-62
references.pmid: 18632568
references.citation: Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9755-60
references.pmid: 12119397
references.citation: J Physiol. 2003 Mar 1;547(Pt 2):509-30
references.pmid: 12562933
references.citation: Mol Vis. 2001 Mar 20;7:71-8
references.pmid: 11262419
references.citation: Vis Neurosci. 2010 Mar;27(1-2):9-17
references.pmid: 20100392
references.citation: J Neurosci. 2007 Dec 19;27(51):14199-204
references.pmid: 18094259
references.citation: J Neurophysiol. 2009 Sep;102(3):1945-55
references.pmid: 19587322
references.citation: Doc Ophthalmol. 1998-1999;95(3-4):187-215
references.pmid: 10532405
references.citation: Invest Ophthalmol Vis Sci. 1995 Jul;36(8):1603-14
references.pmid: 7601641
references.citation: J Physiol. 1990 Feb;421:645-62
references.pmid: 1693403
references.citation: J Neurosci. 2009 May 13;29(19):6088-93
references.pmid: 19439586
references.citation: Invest Ophthalmol Vis Sci. 2010 Feb;51(2):686-93
references.pmid: 19797210
references.citation: J Gen Physiol. 2004 Jun;123(6):729-41
references.pmid: 15173221
references.citation: J Neurosci. 2008 Oct 8;28(41):10443-9
references.pmid: 18842904
references.citation: J Cell Biol. 2008 Nov 3;183(3):485-98
references.pmid: 18981232
references.citation: Bioessays. 2010 Jul;32(7):609-14
references.pmid: 20544736
references.citation: J Biol Chem. 2004 Jan 16;279(3):1581-4
references.pmid: 14625292
references.citation: J Neurosci. 2009 Jul 22;29(29):9301-13
references.pmid: 19625520
references.citation: J Biol Chem. 2005 Aug 12;280(32):29250-5
references.pmid: 15961391
references.citation: J Biol Chem. 1995 Jul 28;270(30):18060-6
references.pmid: 7629115
references.citation: Annu Rev Physiol. 2002;64:153-87
references.pmid: 11826267
references.citation: Neuron. 1998 Jan;20(1):95-102
references.pmid: 9459445
references.citation: Neuron. 2005 May 5;46(3):413-20
references.pmid: 15882641
references.citation: Physiology (Bethesda). 2010 Apr;25(2):72-84
references.pmid: 20430952
references.citation: J Biol Chem. 1993 Jun 5;268(16):11868-73
references.pmid: 8389366