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The Journal of Neuroscience, September 19, 2007, 27(38):10270-10277; doi:10.1523/JNEUROSCI.2494-07.2007

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Cellular/Molecular
N-Terminal Fatty Acylation of Transducin Profoundly Influences Its Localization and the Kinetics of Photoresponse in Rods

Vasily Kerov,¹ William W. Rubin,² Michael Natochin,¹ Nathan A. Melling,² Marie E. Burns,² and Nikolai O. Artemyev¹

¹Department of Molecular Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa 52242, and ²Center for Neuroscience and Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, California 95616

Correspondence should be addressed to Nikolai O. Artemyev, Department of Molecular Physiology and Biophysics, University of Iowa College of Medicine, 5-532 Bowen Science Building, Iowa City, IA 52242. Email: nikolai-artemyev{at}uiowa.edu

N-terminal acylation of the -subunits of heterotrimeric G-proteins is believed to play a major role in regulating the cellular localization and signaling of G-proteins, but physiological evidence has been lacking. To examine the functional significance of N-acylation of a well understood G-protein -subunit, transducin (G_t), we generated transgenic mice that expressed a mutant G_t lacking N-terminal acylation sequence (G_tG2A). Rods expressing G_tG2A showed a severe defect in transducin cellular localization. In contrast to native G_t, which resides in the outer segments of dark-adapted rods, G_tG2A was found predominantly in the inner compartments of the photoreceptor cells. Remarkably, transgenic rods with the outer segments containing G_tG2A at 5–6% of the G_t levels in wild-type rods showed only a sixfold reduction in sensitivity and a threefold decrease in the amplification constant. The much smaller than predicted reduction may reflect an increase in the lateral diffusion of transducin and an increased activation rate by photoexcited rhodopsin or more efficient activation of cGMP phosphodiesterase 6 by G_tG2A; alternatively, nonlinear relationships between concentration and the activation rate of transducin also potentially contribute to the mismatch between the amplification constant and quantitative expression analysis of G_tG2A rods. Furthermore, the G2A mutation reduced the GTPase activity of transducin and resulted in two to three times slower than normal recovery of flash responses of transgenic rods, indicating the role of G_t membrane tethering for its efficient inactivation by the regulator of G-protein signaling 9 GTPase-activating protein complex. Thus, N-acylation is critical for correct compartmentalization of transducin and controls the rate of its deactivation.

Key words: phototransduction; retina; transducin; N-acylation; G-proteins; vision

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Received June 1, 2007; revised July 31, 2007; accepted July 31, 2007.

Correspondence should be addressed to Nikolai O. Artemyev, Department of Molecular Physiology and Biophysics, University of Iowa College of Medicine, 5-532 Bowen Science Building, Iowa City, IA 52242. Email: nikolai-artemyev{at}uiowa.edu

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				E. S. Lobanova, S. Finkelstein, R. Herrmann, Y.-M. Chen, C. Kessler, N. A. Michaud, L. H. Trieu, K. J. Strissel, M. E. Burns, and V. Y. Arshavsky Transducin {gamma}-Subunit Sets Expression Levels of {alpha}- and {beta}-Subunits and Is Crucial for Rod Viability J. Neurosci., March 26, 2008; 28(13): 3510 - 3520. [Abstract] [Full Text] [PDF]

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