| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 266, Issue 28, 18530-18537, Oct, 1991
VYu Arshavsky, MP Gray-Keller and MD Bownds
In rod photoreceptor cells, the light response is triggered by an enzymatic
cascade that causes cGMP levels to fall: excited rhodopsin (Rho*)----rod
G-protein (transducin, Gt)----cGMP-phosphodiesterase (PDE). This results in
the closure of plasma membrane channels that are gated by cGMP. PDE
activation by Gt occurs when GDP bound to the alpha- subunit of Gt (Gt
alpha) is exchanged with free GTP. The interaction of Gt alpha-GTP with the
gamma-subunits of PDE releases their inhibitory action and causes cGMP
hydrolysis. Inactivation is thought to be caused by subsequent hydrolysis
of Gt alpha-GTP by an intrinsic Gt-GTPase activity. Here we report that
there are two portions of Gt in frog rod outer segments (ROS) expressing
different rates of GTP hydrolysis: 19.5 +/- 3 mmol of Gt/mol of Rho,
equivalent to that amount which participates in PDE activation, hydrolyzing
GTP at a rate of approximately 0.6 turnover/s ("fast") and the remaining Gt
(80.5 +/- 3 mmol/mol Rho) hydrolyzing GTP at a rate of 0.058 +/- 0.009
turnover/s. Fast GTPase activity is abolished in the presence of cGMP. This
effect occurs over the physiological range of cGMP concentration changes in
ROS, half-saturating at approximately 2 microM and saturating at 5 microM
cGMP. cGMP-dependent suppression of GTPase is specific for cGMP; cAMP in
millimolar concentration does not affect GTPase, while the poorly
hydrolyzable cGMP analogue, 8-bromo-cGMP, mimics the effect. GTPase
regulation by cGMP is not affected by Ca2+ over the concentration range
5-500 nM, which spans the physiological changes in cytoplasmic Ca2+ in rod
cells. We suggest that the fast cGMP-sensitive GTPase activity is a
property of the Gt that activates PDE. In this model, cGMP serves not only
as a messenger of excitation but also modulates GTPase activity, thereby
mediating negative feedback regulation of the pathway via PDE turnoff: a
light-dependent decrease in cGMP accelerates the hydrolysis of GTP bound to
Gt, resulting in the rapid inactivation of PDE.
cGMP suppresses GTPase activity of a portion of transducin equimolar to phosphodiesterase in frog rod outer segments. Light-induced cGMP decreases as a putative feedback mechanism of the photoresponse
Laboratory of Molecular Biology, University of Wisconsin, Madison 53706.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  V. Kerov, D. Chen, M. Moussaif, Y.-J. Chen, C.-K. Chen, and N. O. Artemyev Transducin Activation State Controls Its Light-dependent Translocation in Rod Photoreceptors J. Biol. Chem., December 9, 2005; 280(49): 41069 - 41076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. G. Muradov and N. O. Artemyev Loss of the Effector Function in a Transducin-alpha Mutant Associated with Nougaret Night Blindness J. Biol. Chem., March 15, 2000; 275(10): 6969 - 6974. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. R. Makino, J. W. Handy, T. Li, and V. Y. Arshavsky The GTPase activating factor for transducin in rod photoreceptors is the complex between RGS9 and type 5 G protein beta subunit PNAS, March 2, 1999; 96(5): 1947 - 1952. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Tsang, M. E. Burns, P. D. Calvert, P. Gouras, D. A. Baylor, S. P. Goff, and V. Y. Arshavsky Role for the Target Enzyme in Deactivation of Photoreceptor G Protein in Vivo Science, October 2, 1998; 282(5386): 117 - 121. [Abstract] [Full Text]
|
|
|
|
|
|
M. Natochin, A. E. Granovsky, and N. O. Artemyev Identification of Effector Residues on Photoreceptor G Protein, Transducin J. Biol. Chem., August 21, 1998; 273(34): 21808 - 21815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Natochin, R. L. McEntaffer, and N. O. Artemyev Mutational Analysis of the Asn Residue Essential for RGS Protein Binding to G-proteins J. Biol. Chem., March 20, 1998; 273(12): 6731 - 6735. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Natochin and N. O. Artemyev Substitution of Transducin Ser202 by Asp Abolishes G-protein/RGS Interaction J. Biol. Chem., February 20, 1998; 273(8): 4300 - 4303. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Wieland, C.-K. Chen, and M. I. Simon The Retinal Specific Protein RGS-r Competes with the gamma Subunit of cGMP Phosphodiesterase for the alpha Subunit of Transducin and Facilitates Signal Termination J. Biol. Chem., April 4, 1997; 272(14): 8853 - 8856. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Faurobert and J. B. Hurley The core domain of a new retina specific RGS protein stimulates the GTPase activity of transducin in vitro PNAS, April 1, 1997; 94(7): 2945 - 2950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Liu, V. Y. Arshavsky, and A. E. Ruoho Interaction Sites of the COOH-terminal Region of the gamma Subunit of cGMP Phosphodiesterase with the GTP-bound alpha Subunit of Transducin J. Biol. Chem., October 25, 1996; 271(43): 26900 - 26907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Z. Slepak, N. O. Artemyev, Y. Zhu, C. L. Dumke, L. Sabacan, J. Sondek, H. E. Hamm, M. D. Bownds, and V. Y. Arshavsky An Effector Site That Stimulates G-protein GTPase in Photoreceptors J. Biol. Chem., June 16, 1995; 270(24): 14319 - 14324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Cook, F. Ghomashchi, M. H. Gelb, S. K. Florio, and J. A. Beavo The delta Subunit of Type 6 Phosphodiesterase Reduces Light-induced cGMP Hydrolysis in Rod Outer Segments J. Biol. Chem., February 9, 2001; 276(7): 5248 - 5255. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
