Arrestin Facilitates Rhodopsin Dephosphorylationin Vivo

Author:

Hsieh Chia-Ling,Yao Yun,Gurevich Vsevolod V.,Chen JeannieORCID

Abstract

Deactivation of G-protein-coupled receptors (GPCRs) involves multiple phosphorylations followed by arrestin binding, which uncouples the GPCR from G-protein activation. Some GPCRs, such as rhodopsin, are reused many times. Arrestin dissociation and GPCR dephosphorylation are key steps in the recycling process.In vitroevidence suggests that visual arrestin (ARR1) binding to light-activated, phosphorylated rhodopsin hinders dephosphorylation. Whether ARR1 binding also affects rhodopsin dephosphorylationin vivois not known. We investigated this using both male and female mice lacking ARR1. Mice were exposed to bright light and placed in darkness for different periods of time, and differently phosphorylated species of rhodopsin were assayed by isoelectric focusing. For WT mice, rhodopsin dephosphorylation was nearly complete by 1 h in darkness. Surprisingly, we observed that, in theArr1KO rods, rhodopsin remained phosphorylated even after 3 h. Delayed dephosphorylation inArr1KO rods cannot be explained by cell stress induced by persistent signaling, since it is not prevented by the removal of transducin, the visual G-protein, nor can it be explained by downregulation of protein phosphatase 2A, the putative rhodopsin phosphatase. We further show that cone arrestin (ARR4), which binds light-activated, phosphorylated rhodopsin poorly, had little effect in enhancing rhodopsin dephosphorylation, whereas mice expressing binding-competent mutant ARR1-3A showed a similar time course of rhodopsin dephosphorylation as WT. Together, these results reveal a novel role of ARR1 in facilitating rhodopsin dephosphorylationin vivo.SIGNIFICANCE STATEMENTG-protein-coupled receptors (GPCRs) are transmembrane proteins used by cells to receive and respond to a broad range of extracellular signals that include neurotransmitters, hormones, odorants, and light (photons). GPCR signaling is terminated by two sequential steps: phosphorylation and arrestin binding. Both steps must be reversed when GPCRs are recycled and reused. Dephosphorylation, which is required for recycling, is an understudied process. Using rhodopsin as a prototypical GPCR, we discovered that arrestin facilitated rhodopsin dephosphorylation in living mice.

Funder

HHS | NIH | National Eye Institute

Publisher

Society for Neuroscience

Subject

General Neuroscience

Cited by 7 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Multiple Functions of Arrestin-1;Reference Module in Neuroscience and Biobehavioral Psychology;2024

2. Phototransduction: Inactivation in Rods;Reference Module in Neuroscience and Biobehavioral Psychology;2024

3. Exome sequencing on 20 probands with early-onset high myopia: identify variants in Retnet genes and interacting of genes in the candidate genes;2023-12-08

4. Posttranslational modifications of proteins in diseased retina;Frontiers in Cellular Neuroscience;2023-03-30

5. Rhodopsin, light-sensor of vision;Progress in Retinal and Eye Research;2023-03

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