title: Phosducin-like protein 1 is essential for G-protein assembly and signaling in retinal rod photoreceptors.
abstract: G-protein β subunits perform essential neuronal functions as part of G-protein βγ and Gβ5-regulators of G-protein signaling (RGS) complexes. Both Gβγ and Gβ5-RGS are obligate dimers that are thought to require the assistance of the cytosolic chaperonin CCT and a cochaperone, phosducin-like protein 1 (PhLP1) for dimer formation. To test this hypothesis in vivo, we deleted the Phlp1 gene in mouse (Mus musculus) retinal rod photoreceptor cells and measured the effects on G-protein biogenesis and visual signal transduction. In the PhLP1-depleted rods, Gβγ dimer formation was decreased 50-fold, resulting in a >10-fold decrease in light sensitivity. Moreover, a 20-fold reduction in Gβ5 and RGS9-1 expression was also observed, causing a 15-fold delay in the shutoff of light responses. These findings conclusively demonstrate in vivo that PhLP1 is required for the folding and assembly of both Gβγ and Gβ5-RGS9.
authors: Department of Chemistry, Brigham Young University, Provo, Utah 84602, USA.
authors: Chun Wan J
authors: CW
authors: Lai
authors: Alexander V
authors: AV
authors: Kolesnikov
authors: Jeanne M
authors: JM
authors: Frederick
authors: Devon R
authors: DR
authors: Blake
authors: Li
authors: L
authors: Jiang
authors: Jubal S
authors: JS
authors: Stewart
authors: Ching-Kang
authors: CK
authors: Chen
authors: Jeffery R
authors: JR
authors: Barrow
authors: Wolfgang
authors: W
authors: Baehr
authors: Vladimir J
authors: VJ
authors: Kefalov
authors: Barry M
authors: BM
authors: Willardson
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena / Q000235:genetics; D015350:Contrast Sensitivity / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism; D044388:GTP-Binding Protein gamma Subunits / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D066298:In Vitro Techniques; D008027:Light; D008564:Membrane Potentials / Q000235:genetics; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation; D012333:RNA, Messenger / Q000378:metabolism; D012160:Retina / Q000166:cytology*; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014792:Visual Acuity / Q000235:genetics
chemical_list: D005136:Eye Proteins; C118981:G-protein Beta gamma; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D008565:Membrane Proteins; C508769:R9AP protein, mouse; D012333:RNA, Messenger; C113752:phosducin-like orphan protein-1; D019204:GTP-Binding Proteins
references: J Neurosci. 2008 Mar 26;28(13):3510-20
references: 18367617
references: Nature. 2000 Feb 3;403(6769):557-60
references: 10676965
references: Vis Neurosci. 1992 Jan;8(1):9-18
references: 1739680
references: J Biol Chem. 2006 Aug 4;281(31):22261-22274
references: 16717095
references: J Neurosci. 2008 Jan 2;28(1):189-98
references: 18171936
references: Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):7962-7
references: 12060742
references: Mol Cell Biol. 2005 Sep;25(18):8393-400
references: 16135826
references: Genesis. 2005 Feb;41(2):73-80
references: 15682388
references: Trends Pharmacol Sci. 2011 Nov;32(11):666-74
references: 21906825
references: Sci Signal. 2011 Aug 23;4(187):er3
references: 21972468
references: EMBO J. 2005 Jun 1;24(11):1965-75
references: 15889144
references: J Neurosci. 2003 Aug 6;23(18):6965-71
references: 12904457
references: Mol Vis. 1999 Dec 29;5:40
references: 10617777
references: J Biol Chem. 2004 Dec 24;279(52):54008-17
references: 15485848
references: Proc Natl Acad Sci U S A. 2003 May 27;100(11):6604-9
references: 12738888
references: J Biol Chem. 2005 May 20;280(20):20042-50
references: 15745879
references: J Biol Chem. 1983 Sep 10;258(17):10495-502
references: 6136509
references: J Neurosci. 2012 Nov 7;32(45):15998-6006
references: 23136436
references: Invest Ophthalmol Vis Sci. 2004 Dec;45(12):4611-6
references: 15557474
references: Mol Cell Proteomics. 2011 Jan;10(1):M110.000570
references: 20852191
references: Prog Neurobiol. 2012 Mar;96(3):304-21
references: 22307060
references: Physiol Rev. 2005 Oct;85(4):1159-204
references: 16183910
references: Pharmacol Rev. 2011 Sep;63(3):728-49
references: 21737532
references: J Biol Chem. 2004 Jan 16;279(3):1581-4
references: 14625292
references: Nat Protoc. 2008;3(6):1056-76
references: 18546598
references: J Biol Chem. 2009 Jun 12;284(24):16386-16399
references: 19376773
references: J Biol Chem. 1994 Mar 25;269(12):9067-73
references: 8132644
references: J Biol Chem. 2006 Jul 21;281(29):20221-32
references: 16702223
references: J Neurosci. 2011 Jun 1;31(22):8067-77
references: 21632928
references: Cell. 2005 Jun 3;121(5):739-48
references: 15935760
references: Prog Mol Biol Transl Sci. 2009;86:205-27
references: 20374717
references: J Gen Physiol. 2007 Sep;130(3):303-12
references: 17724163