TY - JOUR TI - C-terminal threonines and serines play distinct roles in the desensitization of rhodopsin, a G protein-coupled receptor AU - Azevedo, Anthony W AU - Doan, Thuy AU - Moaven, Hormoz AU - Sokal, Iza AU - Baameur, Faiza AU - Vishnivetskiy, Sergey A AU - Homan, Kristoff T AU - Tesmer, John JG AU - Gurevich, Vsevolod V AU - Chen, Jeannie AU - Rieke, Fred A2 - Calabrese, Ronald L VL - 4 PY - 2015 DA - 2015/04/24 SP - e05981 C1 - eLife 2015;4:e05981 DO - 10.7554/eLife.05981 UR - https://doi.org/10.7554/eLife.05981 AB - 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. KW - G-protein-coupled receptor KW - single-photon response KW - arrestin KW - G-protein-coupled receptor kinase JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -