Title | C-terminal threonines and serines play distinct roles in the desensitization of rhodopsin, a G protein-coupled receptor. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Azevedo AW, Doan T, Moaven H, Sokal I, Baameur F, Vishnivetskiy SA, Homan KT, Tesmer JJG, Gurevich VV, Chen J, Rieke F |
Journal | Elife |
Volume | 4 |
Date Published | 2015 Apr 24 |
ISSN | 2050-084X |
Keywords | Animals, Arrestin, Binding Sites, Mice, Mice, Inbred C57BL, Mice, Knockout, Phosphorylation, Receptors, G-Protein-Coupled, Retinal Rod Photoreceptor Cells, Rhodopsin, Serine, Threonine |
Abstract | 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. |
DOI | 10.7554/eLife.05981 |
Alternate Journal | Elife |
PubMed ID | 25910054 |
PubMed Central ID | PMC4438306 |
Grant List | HL086865 / HL / NHLBI NIH HHS / United States HL071818 / HL / NHLBI NIH HHS / United States T32GM-07270 / GM / NIGMS NIH HHS / United States EY11500 / EY / NEI NIH HHS / United States R01 HL086865 / HL / NHLBI NIH HHS / United States T32 GM007270 / GM / NIGMS NIH HHS / United States P30 EY001730 / EY / NEI NIH HHS / United States R01 EY011850 / EY / NEI NIH HHS / United States EY11850 / EY / NEI NIH HHS / United States / / Howard Hughes Medical Institute / United States R01 EY012155 / EY / NEI NIH HHS / United States T32 EY007031 / EY / NEI NIH HHS / United States R01 EY011500 / EY / NEI NIH HHS / United States R01 HL071818 / HL / NHLBI NIH HHS / United States T32EY-07031 / EY / NEI NIH HHS / United States EY12155 / EY / NEI NIH HHS / United States |