title: Retinal cone photoreceptors require phosducin-like protein 1 for G protein complex assembly and signaling.
abstract: G protein β subunits (Gβ) play essential roles in phototransduction as part of G protein βγ (Gβγ) and regulator of G protein signaling 9 (RGS9)-Gβ5 heterodimers. Both are obligate dimers that rely on the cytosolic chaperone CCT and its co-chaperone PhLP1 to form complexes from their nascent polypeptides. The importance of PhLP1 in the assembly process was recently demonstrated in vivo in a retinal rod-specific deletion of the Phlp1 gene. To test whether this is a general mechanism that also applies to other cell types, we disrupted the Phlp1 gene specifically in mouse cones and measured the effects on G protein expression and cone visual signal transduction. In PhLP1-deficient cones, expression of cone transducin (Gt2) and RGS9-Gβ5 subunits was dramatically reduced, resulting in a 27-fold decrease in sensitivity and a 38-fold delay in cone photoresponse recovery. These results demonstrate the essential role of PhLP1 in cone G protein complex formation. Our findings reveal a common mechanism of Gβγ and RGS9-Gβ5 assembly in rods and cones, highlighting the importance of PhLP1 and CCT-mediated Gβ complex formation in G protein signaling.
authors: Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, United States of America.
authors: Christopher M
authors: CM
authors: Tracy
authors: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors: Alexander V
authors: AV
authors: Kolesnikov
authors: Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, United States of America.
authors: Devon R
authors: DR
authors: Blake
authors: Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States of America; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors: Ching-Kang
authors: CK
authors: Chen
authors: Department of Ophthalmology, University of Utah Health Science Center, Salt Lake City, Utah, United States of America; Department of Neurobiology and Anatomy, University of Utah Health Science Center, Salt Lake City, Utah, United States of America; Department of Biology, University of Utah, Salt Lake City, Utah, United States of America.
authors: Wolfgang
authors: W
authors: Baehr
authors: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors: Vladimir J
authors: VJ
authors: Kefalov
authors: Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, United States of America.
authors: Barry M
authors: BM
authors: Willardson
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D044387:GTP-Binding Protein beta Subunits / Q000096:biosynthesis* / Q000235:genetics; D044388:GTP-Binding Protein gamma Subunits / Q000096:biosynthesis* / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization / Q000502:physiology*; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D015293:Transducin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D008565:Membrane Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; C498319:Pdcl protein, mouse; C508769:R9AP protein, mouse; D015293:Transducin