Mechanistic basis for the failure of cone transducin to translocate: why cones are never blinded by light

• Published in: The Journal of neuroscience 2010-05, Vol.30 (20), p.6815-6824
• Main Authors: Lobanova, Ekaterina S, Herrmann, Rolf, Finkelstein, Stella, Reidel, Boris, Skiba, Nikolai P, Deng, Wen-Tao, Jo, Rebecca, Weiss, Ellen R, Hauswirth, William W, Arshavsky, Vadim Y
• Format: Article
• Language: English
• Subjects: 3',5'-Cyclic-GMP Phosphodiesterases - metabolism; Aging - genetics; Aging - metabolism; Animals; Basic-Leucine Zipper Transcription Factors - deficiency; Electroretinography - methods; Eye Proteins; G-Protein-Coupled Receptor Kinase 1 - deficiency; Gene Expression Regulation - genetics; GTP-Binding Protein alpha Subunits - metabolism; GTP-Binding Protein gamma Subunits - metabolism; Light; Light Signal Transduction - genetics; Light Signal Transduction - physiology; Membrane Proteins - deficiency; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Biological; Protein Transport - genetics; Protein Transport - physiology; Retinal Cone Photoreceptor Cells - metabolism; Retinal Rod Photoreceptor Cells - metabolism; RGS Proteins - deficiency; Transducin - metabolism
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.0613-10.2010

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.