title: Replacing the rod with the cone transducin subunit decreases sensitivity and accelerates response decay.
abstract: Cone vision is less sensitive than rod vision. Much of this difference can be attributed to the photoreceptors themselves, but the reason why the cones are less sensitive is still unknown. Recent recordings indicate that one important factor may be a difference in the rate of activation of cone transduction; that is, the rising phase of the cone response per bleached rhodopsin molecule (Rh*) has a smaller slope than the rising phase of the rod response per Rh*, perhaps because some step between Rh* and activation of the phosphodiesterase 6 (PDE6) effector molecule occurs with less gain. Since rods and cones have different G-protein alpha subunits, and since this subunit (Talpha) plays a key role both in the interaction of G-protein with Rh* and the activation of PDE6, we investigated the mechanism of the amplification difference by expressing cone Talpha in rod Talpha-knockout rods to produce so-called GNAT2C mice. We show that rods in GNAT2C mice have decreased sensitivity and a rate of activation half that of wild-type (WT) mouse rods. Furthermore, GNAT2C responses recover more rapidly than WT responses with kinetic parameters resembling those of native mouse cones. Our results show for the first time that part of the difference in sensitivity and response kinetics between rods and cones may be the result of a difference in the G-protein alpha subunit. They also indicate more generally that the molecular nature of G-protein alpha may play an important role in the kinetics of G-protein cascades for metabotropic receptors throughout the body.
authors.affiliation: Department of Integrative Biology and Physiology, University of California Los Angeles, 3836 Life Sciences Building, Los Angeles 90095-1606, USA.
authors.forename: C-K
authors.initials: CK
authors.lastname: Chen
authors.forename: M L
authors.initials: ML
authors.lastname: Woodruff
authors.forename: F S
authors.initials: FS
authors.lastname: Chen
authors.forename: H
authors.initials: H
authors.lastname: Shim
authors.forename: M C
authors.initials: MC
authors.lastname: Cilluffo
authors.forename: G L
authors.initials: GL
authors.lastname: Fain
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000235:genetics; D005136:Eye Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D044385:GTP-Binding Protein alpha Subunits / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D020962:Heterotrimeric GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010775:Photic Stimulation / Q000379:methods; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D011930:Reaction Time / Q000235:genetics; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism* / Q000473:pathology; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism* / Q000473:pathology; D012680:Sensitivity and Specificity; D015293:Transducin / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics
chemical_list: D005136:Eye Proteins; D044385:GTP-Binding Protein alpha Subunits; C515337:Gnat2 protein, mouse; D021122:Protein Subunits; D020962:Heterotrimeric GTP-Binding Proteins; D015293:Transducin