C-terminal threonines and serines play distinct roles in the desensitization of rhodopsin, a G protein-coupled receptor
Rod photoreceptors generate measurable responses to single-photon activation of individual molecules of the G protein-coupled receptor (GPCR), rhodopsin. Timely rhodopsin desensitization depends on phosphorylation and arrestin binding, which quenches G protein activation. Rhodopsin phosphorylation h...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-04-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/05981 |
| _version_ | 1811235838992842752 |
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| author | Anthony W Azevedo Thuy Doan Hormoz Moaven Iza Sokal Faiza Baameur Sergey A Vishnivetskiy Kristoff T Homan John JG Tesmer Vsevolod V Gurevich Jeannie Chen Fred Rieke |
| author_facet | Anthony W Azevedo Thuy Doan Hormoz Moaven Iza Sokal Faiza Baameur Sergey A Vishnivetskiy Kristoff T Homan John JG Tesmer Vsevolod V Gurevich Jeannie Chen Fred Rieke |
| author_sort | Anthony W Azevedo |
| collection | DOAJ |
| description | Rod photoreceptors generate measurable responses to single-photon activation of individual molecules of the G protein-coupled receptor (GPCR), 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 GPCR activity. |
| first_indexed | 2024-04-12T11:58:52Z |
| format | Article |
| id | doaj.art-4edccd85553d48d8a0ead6c6fbec1158 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T11:58:52Z |
| publishDate | 2015-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-4edccd85553d48d8a0ead6c6fbec11582022-12-22T03:33:54ZengeLife Sciences Publications LtdeLife2050-084X2015-04-01410.7554/eLife.05981C-terminal threonines and serines play distinct roles in the desensitization of rhodopsin, a G protein-coupled receptorAnthony W Azevedo0Thuy Doan1Hormoz Moaven2Iza Sokal3Faiza Baameur4Sergey A Vishnivetskiy5Kristoff T Homan6John JG Tesmer7Vsevolod V Gurevich8https://orcid.org/0000-0002-3950-5351Jeannie Chen9Fred Rieke10Department of Physiology and Biophysics, University of Washington, Seattle, United StatesDepartment of Ophthalmology, University of Washington, Seattle, United StatesDepartments of Cell & Neurobiology and Ophthalmology, Zilkha Neurogenetic Institute, Keck School of Medicine of University of Southern California, Los Angeles, United StatesDepartment of Physiology and Biophysics, University of Washington, Seattle, United StatesDepartment of Pharmacology, Vanderbilt University School of Medicine, Nashville, United StatesDepartment of Pharmacology, Vanderbilt University School of Medicine, Nashville, United StatesLife Sciences Institute, Departments of Pharmacology and Biological Chemistry, University of Michigan, Ann Arbor, United StatesLife Sciences Institute, Departments of Pharmacology and Biological Chemistry, University of Michigan, Ann Arbor, United StatesDepartment of Pharmacology, Vanderbilt University School of Medicine, Nashville, United StatesDepartments of Cell & Neurobiology and Ophthalmology, Zilkha Neurogenetic Institute, Keck School of Medicine of University of Southern California, Los Angeles, United StatesDepartment of Physiology and Biophysics, University of Washington, Seattle, United States; Howard Hughes Medical Institute, University of Washington, Seattle, United StatesRod photoreceptors generate measurable responses to single-photon activation of individual molecules of the G protein-coupled receptor (GPCR), 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 GPCR activity.https://elifesciences.org/articles/05981G-protein-coupled receptorsingle-photon responsearrestinG-protein-coupled receptor kinase |
| spellingShingle | Anthony W Azevedo Thuy Doan Hormoz Moaven Iza Sokal Faiza Baameur Sergey A Vishnivetskiy Kristoff T Homan John JG Tesmer Vsevolod V Gurevich Jeannie Chen Fred Rieke C-terminal threonines and serines play distinct roles in the desensitization of rhodopsin, a G protein-coupled receptor eLife G-protein-coupled receptor single-photon response arrestin G-protein-coupled receptor kinase |
| title | C-terminal threonines and serines play distinct roles in the desensitization of rhodopsin, a G protein-coupled receptor |
| title_full | C-terminal threonines and serines play distinct roles in the desensitization of rhodopsin, a G protein-coupled receptor |
| title_fullStr | C-terminal threonines and serines play distinct roles in the desensitization of rhodopsin, a G protein-coupled receptor |
| title_full_unstemmed | C-terminal threonines and serines play distinct roles in the desensitization of rhodopsin, a G protein-coupled receptor |
| title_short | C-terminal threonines and serines play distinct roles in the desensitization of rhodopsin, a G protein-coupled receptor |
| title_sort | c terminal threonines and serines play distinct roles in the desensitization of rhodopsin a g protein coupled receptor |
| topic | G-protein-coupled receptor single-photon response arrestin G-protein-coupled receptor kinase |
| url | https://elifesciences.org/articles/05981 |
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