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J. Biol. Chem., Vol. 280, Issue 49, 41069-41076, December 9, 2005
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1
From the
Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa 52242 and the
Department of Biochemistry, Virginia Commonwealth University, Richmond, Virginia 23298
Light-dependent redistribution of transducin between the rod outer segments (OS) and other photoreceptor compartments including the inner segments (IS) and synaptic terminals (ST) is recognized as a critical contributing factor to light and dark adaptation. The mechanisms of light-induced transducin translocation to the IS/ST and its return to the OS during dark adaptation are not well understood. We have probed these mechanisms by examining light-dependent localizations of the transducin-
subunit (Gt
)in mice lacking the photoreceptor GAP-protein RGS9, or expressing the GTPase-deficient mutant Gt
Q200L. An illumination threshold for the Gt
movement out of the OS is lower in the RGS9 knockout mice, indicating that the fast inactivation of transducin in the wild-type mice limits its translocation to the IS/ST. Transgenic Gt
Q200L mice have significantly diminished levels of proteins involved in cGMP metabolism in rods, most notably the PDE6 catalytic subunits, and severely reduced sensitivity to light. Similarly to the native Gt
, the Gt
Q200L mutant is localized to the IS/ST compartment in light-adapted transgenic mice. However, the return of Gt
Q200L to the OS during dark adaptation is markedly slower than normal. Thus, the light-dependent translocations of transducin are controlled by the GTP-hydrolysis on Gt
, and apparently, do not require Gt
interaction with RGS9 and PDE6.
Received for publication, August 10, 2005 , and in revised form, October 3, 2005.
* This work was supported by National Institutes of Health Grants EY12682 (to N. O. A.) and EY13811 (to C.-K. C.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 To whom correspondence should be addressed: Dept. of Physiology and Biophysics, University of Iowa College of Medicine, 5-532 Bowen Science Bldg., 51 Newton Rd., Iowa City, IA 52242. Tel.: 319-335-7864; Fax: 319-335-7330; E-mail: nikolai-artemyev{at}uiowa.edu.
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