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

Azevedo AW, Doan T, Moaven H, Sokal I, Baameur F, Vishnivetskiy SA, Homan KT, Tesmer JJ, Gurevich VV, Chen J, Rieke F
Elife. 2015 4

PMID: 25910054 · PMCID: PMC4438306 · DOI:10.7554/eLife.05981

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.

MeSH Terms (12)

Animals Arrestin Binding Sites Mice Mice, Inbred C57BL Mice, Knockout Phosphorylation Receptors, G-Protein-Coupled Retinal Rod Photoreceptor Cells Rhodopsin Serine Threonine

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