title: The loss of the PDE6 deactivating enzyme, RGS9, results in precocious light adaptation at low light levels.
abstract: The GTPase activating protein, RGS9-1, is vital for the deactivation and regulation of the phototransduction cascade (C. K. Chen et al., 2000; C. W. Cowan, R. N. Fariss, I. Sokal, K. Palczewski, & T. G. Wensel, 1998; W. He, C. W. Cowan, & T. G. Wensel, 1998; A. L. Lyubarsky et al., 2001). Its loss through genetic defects in humans has been linked to a slow recovery to changes in illumination (K. M. Nishiguchi et al., 2004). Such a deficit is to be expected because RGS9-1 normally speeds up the deactivation of the activated phosphodiesterase effector molecule, PDE6*, and thus accelerates the turning off of the visual response. Paradoxically, however, we find that the cone response in an observer lacking RGS9-1 is faster at lower light levels than it is in a normal observer. Though surprising, this result is nonetheless consistent with molecular models of light adaptation (e.g., E. N. Pugh, S. Nikonov, & T. D. Lamb, 1999), which predict that the excess of PDE6* resulting from the loss of RGS9-1 will shorten the visual integration time and speed up the visual response at inappropriately low light levels. The gain in speed caused by the superfluity of PDE6* at lower light levels compensates for the loss caused by its slow deactivation; thus quickening the response relative to that in the normal. As the light level is increased and the PDE6* concentration in the normal rises relative to that in the observer lacking RGS9-1, the temporal advantage of the latter is soon lost, leaving only the deficit due to delayed deactivation.
authors.affiliation: Institute of Ophthalmology, University College London, London, UK. a.stockman@ucl.ac.uk
authors.forename: Andrew
authors.initials: A
authors.lastname: Stockman
authors.forename: Hannah E
authors.initials: HE
authors.lastname: Smithson
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Webster
authors.forename: Graham E
authors.initials: GE
authors.lastname: Holder
authors.forename: Naheed A
authors.initials: NA
authors.lastname: Rana
authors.forename: Caterina
authors.initials: C
authors.lastname: Ripamonti
authors.forename: Lindsay T
authors.initials: LT
authors.lastname: Sharpe
mesh_terms: D000221:Adaptation, Ocular / Q000502:physiology*; D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D015350:Contrast Sensitivity / Q000502:physiology*; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D005425:Flicker Fusion; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D020125:Mutation, Missense; D012160:Retina / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; C464657:RGS9BP protein, human; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6