Mechanistic basis for the failure of cone transducin to translocate: why cones are never blinded by light.
The remarkable ability of our vision to function under ever-changing conditions of ambient illumination is mediated by multiple molecular mechanisms regulating the light sensitivity of rods and cones. One such mechanism involves massive translocation of signaling proteins, including the G-protein transducin, into and out of the light-sensitive photoreceptor outer segment compartment. Transducin translocation extends the operating range of rods, but in cones transducin never translocates, which is puzzling because cones typically function in much brighter light than rods. Using genetically manipulated mice in which the rates of transducin activation and inactivation were altered, we demonstrate that, like in rods, transducin translocation in cones can be triggered when transducin activation exceeds a critical level, essentially saturating the photoresponse. However, this level is never achieved in wild-type cones: their superior ability to tightly control the rates of transducin activation and inactivation, responsible for avoiding saturation by light, also accounts for the prevention of transducin translocation at any light intensity.
Lobanova
Ekaterina S
ES
Albert Eye Research Institute, Duke University, Durham, North Carolina 27710, USA.
Herrmann
Rolf
R
Finkelstein
Stella
S
Reidel
Boris
B
Skiba
Nikolai P
NP
Deng
Wen-Tao
WT
Jo
Rebecca
R
Weiss
Ellen R
ER
Hauswirth
William W
WW
Arshavsky
Vadim Y
VY
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism; D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000172:deficiency; D004596:Electroretinography / Q000379:methods; D005136:Eye Proteins; D051606:G-Protein-Coupled Receptor Kinase 1 / Q000172:deficiency; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism; D044388:GTP-Binding Protein gamma Subunits / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D008027:Light; D055537:Light Signal Transduction / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000172:deficiency; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D020710:RGS Proteins / Q000172:deficiency; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism; D015293:Transducin / Q000378:metabolism*
D050976:Basic-Leucine Zipper Transcription Factors; D005136:Eye Proteins; D044385:GTP-Binding Protein alpha Subunits; D044388:GTP-Binding Protein gamma Subunits; D008565:Membrane Proteins; C084884:Nrl protein, mouse; C508769:R9AP protein, mouse; D020710:RGS Proteins; C116925:regulator of g-protein signaling 9; D051606:G-Protein-Coupled Receptor Kinase 1; C496762:Grk1 protein, mouse; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D015293:Transducin