HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental data All Versions of this Article: 579/2/303    most recent jphysiol.2006.121772v2 jphysiol.2006.121772v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tsang, S. H. Articles by Fain, G. L. Search for Related Content PubMed PubMed Citation Articles by Tsang, S. H. Articles by Fain, G. L. Related Collections Cellular

¹ Brown Glaucoma Laboratory, Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
² Department of Physiological Science, UCLA, Los Angeles, CA 90095-1606, USA
³ Microscopic Techniques Laboratory, Brain Research Institute, Gonda 1346, UCLA, Los Angeles, CA 90095-1761, USA
⁴ Jules Stein Eye Institute, UCLA School of Medicine, Los Angeles, CA 90095-7000, USA

The phosphodiesterase 6 (PDE6) inhibitory subunit of the rod PDE6 effector enzyme plays a central role in the turning on and off of the visual transduction cascade, since binding of PDE6 to the transducin subunit (T) initiates the hydrolysis of the second messenger cGMP, and PDE6 in association with RGS9-1 and the other GAP complex proteins (G5, R9AP) accelerates the conversion of TGTP to TGDP, the rate-limiting step in the decay of the rod light response. Several studies have shown that PDE6 can be phosphorylated at two threonines, T22 and T35, and have proposed that phosphorylation plays some role in the physiology of the rod. We have examined this possibility by constructing mice in which T22 and/or T35 were replaced with alanines. Our results show that T35A rod responses rise and decay more slowly and are less sensitive to light than wild-type (WT). T22A responses show no significant difference in initial time course with WT but decay more rapidly, especially at dimmer intensities. When the T22A mutation is added to T35A, double mutant rods no longer showed the prolonged decay of T35A rods but remained slower than WT in initial time course. Our experiments suggest that the polycationic domain of PDE6 containing these two phosphorylation sites can influence the rate of PDE6 activation and deactivation and raise the possibility that phosphorylation or dephosphorylation of PDE6 could modify the time course of transduction, thereby influencing the wave form of the light response.

(Received 25 September 2006; accepted after revision 30 November 2006; first published online 30 November 2006)
Corresponding author G. L. Fain: Department of Physiological Science, University of California Los Angeles, 3836 Life Sciences, Los Angeles, CA 90095-1606, USA. Email: gfain{at}ucla.edu

This article has been cited by other articles:

				M. L. Woodruff, K. M. Janisch, I. V. Peshenko, A. M. Dizhoor, S. H. Tsang, and G. L. Fain Modulation of Phosphodiesterase6 Turnoff during Background Illumination in Mouse Rod Photoreceptors J. Neurosci., February 27, 2008; 28(9): 2064 - 2074. [Abstract] [Full Text] [PDF]