The loss of the PDE6 deactivating enzyme, RGS9, results in precocious light adaptation at low light levels

Stockman, A.; Smithson, H.E.; Webster, A.R.; Holder, G.E.; Rana, N.A.; Ripamonti, C.; Sharpe, L.T.

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.

Citation

Stockman, A., Smithson, H., Webster, A., Holder, G., Rana, N., Ripamonti, C., & Sharpe, L. (2008). The loss of the PDE6 deactivating enzyme, RGS9, results in precocious light adaptation at low light levels. Journal of Vision, 8(1), https://doi.org/10.1167/8.1.10

• Journal Article Type: Article
• Publication Date: Jan 18, 2008
• Deposit Date: Oct 25, 2011
• Journal: Journal of Vision
• Electronic ISSN: 1534-7362
• Publisher: Association for Research in Vision and Ophthalmology
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 1
• DOI: https://doi.org/10.1167/8.1.10
• Keywords: Vision, Cone photoreceptor, Visual transduction, Photopigment,Bradyopsia, RGS9, PDE6, Light adaptation.
• Public URL: https://durham-repository.worktribe.com/output/1564601