Journal article
N-Terminal Fatty Acylation of Transducin Profoundly Influences Its Localization and the Kinetics of Photoresponse in Rods
The Journal of neuroscience, Vol.27(38), pp.10270-10277
09/19/2007
DOI: 10.1523/JNEUROSCI.2494-07.2007
PMCID: PMC6672661
PMID: 17881533
Abstract
N-terminal acylation of the α-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 α-subunit, transducin (Gα
t
), we generated transgenic mice that expressed a mutant Gα
t
lacking N-terminal acylation sequence (Gα
t
G2A). Rods expressing Gα
t
G2A showed a severe defect in transducin cellular localization. In contrast to native Gα
t
, which resides in the outer segments of dark-adapted rods, Gα
t
G2A was found predominantly in the inner compartments of the photoreceptor cells. Remarkably, transgenic rods with the outer segments containing Gα
t
G2A at 5–6% of the Gα
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 Gα
t
G2A; 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 Gα
t
G2A 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 Gα
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.
Details
- Title: Subtitle
- N-Terminal Fatty Acylation of Transducin Profoundly Influences Its Localization and the Kinetics of Photoresponse in Rods
- Creators
- Vasily Kerov - Department of Molecular Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa 52242, andWilliam W Rubin - Center for Neuroscience and Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, California 95616Michael Natochin - Department of Molecular Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa 52242, andNathan A Melling - Center for Neuroscience and Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, California 95616Marie E Burns - Center for Neuroscience and Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, California 95616Nikolai O Artemyev - Department of Molecular Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa 52242, and
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.27(38), pp.10270-10277
- Publisher
- Society for Neuroscience
- DOI
- 10.1523/JNEUROSCI.2494-07.2007
- PMID
- 17881533
- PMCID
- PMC6672661
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Language
- English
- Date published
- 09/19/2007
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
- Record Identifier
- 9984070421002771
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