title: Functional comparison of rod and cone Gα(t) on the regulation of light sensitivity.
abstract: The signaling cascades mediated by G protein-coupled receptors (GPCRs) exhibit a wide spectrum of spatial and temporal response properties to fulfill diverse physiological demands. However, the mechanisms that shape the signaling response of the GPCR are not well understood. In this study, we replaced cone transducin α (cTα) for rod transducin α (rTα) in rod photoreceptors of transgenic mice, which also express S opsin, to evaluate the role of Gα subtype on signal amplification from different GPCRs in the same cell; such analysis may explain functional differences between retinal rod and cone photoreceptors. We showed that ectopically expressed cTα 1) forms a heterotrimeric complex with rod Gβ(1)γ(1), 2) substitutes equally for rTα in generating photoresponses initiated by either rhodopsin or S-cone opsin, and 3) exhibited similar light-activated translocation as endogenous rTα in rods and endogenous cTα in cones. Thus, rTα and cTα appear functionally interchangeable. Interestingly, light sensitivity appeared to correlate with the concentration of cTα when expression is reduced below 35% of normal. However, quantification of endogenous cTα concentration in cones showed a higher level to rTα in rods. Thus, reduced sensitivity in cones cannot be explained by reduced coupling efficiency between the GPCR and G protein or a lower concentration of G protein in cones versus rods.
authors.affiliation: Department of Cell and Neurobiology, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Mao
authors.forename: K J
authors.initials: KJ
authors.lastname: Miyagishima
authors.forename: Yun
authors.initials: Y
authors.lastname: Yao
authors.forename: Brian
authors.initials: B
authors.lastname: Soreghan
authors.forename: Alapakkam P
authors.initials: AP
authors.lastname: Sampath
authors.forename: Jeannie
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; 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; D008027:Light; D055537:Light Signal Transduction; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D008954:Models, Biological; D055355:Opsins / Q000378:metabolism; D010858:Pigmentation; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012160:Retina / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000166:cytology / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000378:metabolism*; D012243:Rhodopsin / Q000378:metabolism; D015398:Signal Transduction; D015293:Transducin / Q000235:genetics / Q000502:physiology*
chemical_list: D018076:DNA, Complementary; C118981:G-protein Beta gamma; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D055355:Opsins; D043562:Receptors, G-Protein-Coupled; D012243:Rhodopsin; D019204:GTP-Binding Proteins; D015293:Transducin