title: Cones respond to light in the absence of transducin β subunit.
abstract: Mammalian cones respond to light by closing a cGMP-gated channel via a cascade that includes a heterotrimeric G-protein, cone transducin, comprising Gαt2, Gβ3 and Gγt2 subunits. The function of Gβγ in this cascade has not been examined. Here, we investigate the role of Gβ3 by assessing cone structure and function in Gβ3-null mouse (Gnb3(-/-)). We found that Gβ3 is required for the normal expression of its partners, because in the Gnb3(-/-) cone outer segments, the levels of Gαt2 and Gγt2 are reduced by fourfold to sixfold, whereas other components of the cascade remain unaltered. Surprisingly, Gnb3(-/-) cones produce stable responses with normal kinetics and saturating response amplitudes similar to that of the wild-type, suggesting that cone phototransduction can function efficiently without a Gβ subunit. However, light sensitivity was reduced by approximately fourfold in the knock-out cones. Because the reduction in sensitivity was similar in magnitude to the reduction in Gαt2 level in the cone outer segment, we conclude that activation of Gαt2 in Gnb3(-/-) cones proceeds at a rate approximately proportional to its outer segment concentration, and that activation of phosphodiesterase and downstream cascade components is normal. These results suggest that the main role of Gβ3 in cones is to establish optimal levels of transducin heteromer in the outer segment, thereby indirectly contributing to robust response properties.
authors.affiliation: Departments of Neuroscience and Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USA. sergein@mail.med.upenn.edu
authors.forename: Sergei S
authors.initials: SS
authors.lastname: Nikonov
authors.forename: Arkady
authors.initials: A
authors.lastname: Lyubarsky
authors.forename: Marie E
authors.initials: ME
authors.lastname: Fina
authors.forename: Elena S
authors.initials: ES
authors.lastname: Nikonova
authors.forename: Abhishek
authors.initials: A
authors.lastname: Sengupta
authors.forename: Chidambaram
authors.initials: C
authors.lastname: Chinniah
authors.forename: Xi-Qin
authors.initials: XQ
authors.lastname: Ding
authors.forename: Robert G
authors.initials: RG
authors.lastname: Smith
authors.forename: Edward N
authors.initials: EN
authors.lastname: Pugh
authors.forename: Noga
authors.initials: N
authors.lastname: Vardi
authors.forename: Anuradha
authors.initials: A
authors.lastname: Dhingra
mesh_terms: D000818:Animals; D003116:Color; D005260:Female; D050485:GABA Plasma Membrane Transport Proteins / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008959:Models, Neurological; D010775:Photic Stimulation; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology*; D055214:Retinal Photoreceptor Cell Outer Segment / Q000502:physiology; D015293:Transducin / Q000235:genetics* / Q000502:physiology; D014466:Ultraviolet Rays; D014785:Vision, Ocular / Q000502:physiology*
chemical_list: C454420:G-protein beta3 subunit; D050485:GABA Plasma Membrane Transport Proteins; C490439:Slc6a12 protein, mouse; D049452:Green Fluorescent Proteins; D020962:Heterotrimeric GTP-Binding Proteins; D015293:Transducin