1. Structural Biology and Molecular Biophysics
  2. Neuroscience
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C-terminal threonines and serines play distinct roles in the desensitization of rhodopsin, a G protein-coupled receptor

  1. Anthony W Azevedo
  2. Thuy Doan
  3. Hormoz Moaven
  4. Iza Sokal
  5. Faiza Baameur
  6. Sergey A Vishnivetskiy
  7. Kristoff T Homan
  8. John J G Tesmer
  9. Vsevolod V Gurevich
  10. Jeannie Chen
  11. Fred Rieke  Is a corresponding author
  1. University of Washington, United States
  2. Keck School of Medicine of University of Southern California, United States
  3. Vanderbilt University School of Medicine, United States
  4. University of Michigan, United States
Research Article
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Cite this article as: eLife 2015;4:e05981 doi: 10.7554/eLife.05981

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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Author details

  1. Anthony W Azevedo

    Department of Physiology and Biophysics, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Thuy Doan

    Department of Ophthalmology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Hormoz Moaven

    Departments of Cell & Neurobiology and Ophthalmology, Zilkha Neurogenetic Institute, Keck School of Medicine of University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Iza Sokal

    Department of Physiology and Biophysics, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Faiza Baameur

    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Sergey A Vishnivetskiy

    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Kristoff T Homan

    Life Sciences Institute, Departments of Pharmacology and Biological Chemistry, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. John J G Tesmer

    Life Sciences Institute, Departments of Pharmacology and Biological Chemistry, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Vsevolod V Gurevich

    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.

  10. Jeannie Chen

    Departments of Cell & Neurobiology and Ophthalmology, Zilkha Neurogenetic Institute, Keck School of Medicine of University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  11. Fred Rieke

    Department of Physiology and Biophysics, University of Washington, Seattle, United States
    For correspondence
    rieke@u.washington.edu
    Competing interests
    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.

Reviewing Editor

  1. Ronald L Calabrese, Emory University, United States

Publication history

  1. Received: December 9, 2014
  2. Accepted: April 23, 2015
  3. Accepted Manuscript published: April 24, 2015 (version 1)
  4. Version of Record published: May 20, 2015 (version 2)

Copyright

© 2015, Azevedo et al.

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.

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