C-terminal threonines and serines play distinct roles in the desensitization of rhodopsin, a G protein-coupled receptor

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Abstract

Rod photoreceptors generate measurable responses to single-photon activation of individual molecules of the G-protein-coupled receptor, rhodopsin. Timely rhodopsin desensitization depends on phosphorylation and arrestin binding, which quenches G-protein activation. Rhodopsin phosphorylation has been measured biochemically at C-terminal serine residues, suggesting that these residues are critical for producing fast, low noise responses. The role of native threonine residues is unclear. We compared single-photon responses from rhodopsin lacking native serine or threonine phosphorylation sites. Contrary to expectation, serine-only rhodopsin generated prolonged step-like single-photon responses that terminated abruptly and randomly, whereas threonine-only rhodopsin generated responses that were only modestly slower than normal. We show that the step-like responses of serine-only rhodopsin reflect slow and stochastic arrestin binding. Thus, threonine sites play a privileged role in promoting timely arrestin binding and rhodopsin desensitization. Similar coordination of phosphorylation and arrestin binding may more generally permit tight control of the duration of G-protein-coupled receptor activity.

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Anthony W Azevedo

Department of Physiology and Biophysics, University of Washington, Seattle, United States

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The authors declare that no competing interests exist.
Thuy Doan

Department of Ophthalmology, University of Washington, Seattle, United States

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The authors declare that no competing interests exist.
Hormoz Moaven

Departments of Cell & Neurobiology and Ophthalmology, Zilkha Neurogenetic Institute, Keck School of Medicine of University of Southern California, Los Angeles, United States

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The authors declare that no competing interests exist.
Iza Sokal

Department of Physiology and Biophysics, University of Washington, Seattle, United States

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The authors declare that no competing interests exist.
Faiza Baameur

Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, United States

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Sergey A Vishnivetskiy

Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, United States

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Kristoff T Homan

Life Sciences Institute, Departments of Pharmacology and Biological Chemistry, University of Michigan, Ann Arbor, United States

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John J G Tesmer

Life Sciences Institute, Departments of Pharmacology and Biological Chemistry, University of Michigan, Ann Arbor, United States

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Vsevolod V Gurevich

Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, United States

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Jeannie Chen

Departments of Cell & Neurobiology and Ophthalmology, Zilkha Neurogenetic Institute, Keck School of Medicine of University of Southern California, Los Angeles, United States

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The authors declare that no competing interests exist.
Fred Rieke

Department of Physiology and Biophysics, University of Washington, Seattle, United States

For correspondence
rieke@u.washington.edu

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The authors declare that no competing interests exist.

Ethics

Animal experimentation: This work was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All procedures followed protocols approved by the Institutional Animal Care and Use Committee (protocol 3030-01) of the University of Washington.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.