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

J. Biol. Chem., Vol. 282, Issue 44, 32075-32083, November 2, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/44/32075    most recent M706057200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vishnivetskiy, S. A. Articles by Gurevich, V. V. Search for Related Content PubMed PubMed Citation Articles by Vishnivetskiy, S. A. Articles by Gurevich, V. V. Social Bookmarking                      What's this?

Regulation of Arrestin Binding by Rhodopsin Phosphorylation Level^*

Sergey A. Vishnivetskiy, Dayanidhi Raman, Junhua Wei, Matthew J. Kennedy, James B. Hurley¹, and Vsevolod V. Gurevich²

From the Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232 and the Department of Biochemistry, University of Washington, Seattle, Washington 98195

Arrestins ensure the timely termination of receptor signaling. The role of rhodopsin phosphorylation in visual arrestin binding was established more than 20 years ago, but the effects of the number of receptor-attached phosphates on this interaction remain controversial. Here we use purified rhodopsin fractions with carefully quantified content of individual phosphorylated rhodopsin species to elucidate the impact of phosphorylation level on arrestin interaction with three biologically relevant functional forms of rhodopsin: light-activated and dark phosphorhodopsin and phospho-opsin. We found that a single receptor-attached phosphate does not facilitate arrestin binding, two are necessary to induce high affinity interaction, and three phosphates fully activate arrestin. Higher phosphorylation levels do not increase the stability of arrestin complex with light-activated rhodopsin but enhance its binding to the dark phosphorhodopsin and phospho-opsin. The complex of arrestin with hyperphosphorylated light-activated rhodopsin is less sensitive to high salt and appears to release retinal faster. These data suggest that arrestin likely quenches rhodopsin signaling after the third phosphate is added by rhodopsin kinase. The complex of arrestin with heavily phosphorylated rhodopsin, which appears to form in certain disease states, has distinct characteristics that may contribute to the phenotype of these visual disorders.

Received for publication, July 24, 2007 , and in revised form, August 27, 2007.

^* This work was supported by National Institutes of Health Grants EY11500 (to V. V. G.) and EY06641 (to J. B. H.). 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 may be addressed. Tel.: 206-543-2871; Fax: 206-685-2320; E-mail: jbhhh{at}u.washington.edu. ² To whom correspondence may be addressed: Dept. of Pharmacology, Vanderbilt University, 2200 Pierce Ave., PRB 418, Nashville, TN 37232. Tel.: 615-322-7070; Fax: 615-343-6532; E-mail: vsevolod.gurevich{at}vanderbilt.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. M.C. van Der Lee, M. Bras, C. J. van Koppen, and G. J.R. Zaman {beta}-Arrestin Recruitment Assay for the Identification of Agonists of the Sphingosine 1-Phosphate Receptor EDG1 J Biomol Screen, December 1, 2008; 13(10): 986 - 998. [Abstract] [PDF]

				A. M. Dizhoor, M. L. Woodruff, E. V. Olshevskaya, M. C. Cilluffo, M. C. Cornwall, P. A. Sieving, and G. L. Fain Night Blindness and the Mechanism of Constitutive Signaling of Mutant G90D Rhodopsin J. Neurosci., November 5, 2008; 28(45): 11662 - 11672. [Abstract] [Full Text] [PDF]

				V. V. Gurevich and E. V. Gurevich Rich Tapestry of G Protein-Coupled Receptor Signaling and Regulatory Mechanisms Mol. Pharmacol., August 1, 2008; 74(2): 312 - 316. [Abstract] [Full Text] [PDF]

				B. W. Jones and P. M. Hinkle Arrestin Binds to Different Phosphorylated Regions of the Thyrotropin-Releasing Hormone Receptor with Distinct Functional Consequences Mol. Pharmacol., July 1, 2008; 74(1): 195 - 202. [Abstract] [Full Text] [PDF]