Arginylation Regulates G-protein Signaling in the Retina.

Marie E Fina,Pavan Vedula,Hsin-Yao Tang,Anna Kashina,Dawei W Dong,Junling Wang

doi:10.3389/fcell.2021.807345

Marie E Fina, Pavan Vedula + Show 4 more

Open Access

https://doi.org/10.3389/fcell.2021.807345

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Abstract

Arginylation is a post-translational modification mediated by the arginyltransferase (Ate1). We recently showed that conditional deletion of Ate1 in the nervous system leads to increased light-evoked response sensitivities of ON-bipolar cells in the retina, indicating that arginylation regulates the G-protein signaling complexes of those neurons and/or photoreceptors. However, none of the key players in the signaling pathway were previously shown to be arginylated. Here we show that Gαt1, Gβ1, RGS6, and RGS7 are arginylated in the retina and RGS6 and RGS7 protein levels are elevated in Ate1 knockout, suggesting that arginylation plays a direct role in regulating their protein level and the G-protein-mediated responses in the retina.

Highlights

Arginylation is a post-translational modification that has been implicated in a large number of key physiological processes
This work represents the first comprehensive analysis of arginylation of the components of G-protein signaling in the retina, including G-protein coupled receptors (GPCRs), G-proteins, and Regulator of G-protein signaling (RGS) proteins
We find putative arginylation sites on the aspartate and glutamate side chains of Gαt1, Gβ1, RGS6, and RGS7, and no N-terminal arginylation among the proteins involved in the G-protein signaling in the retina

Summary

Introduction

Arginylation is a post-translational modification that has been implicated in a large number of key physiological processes (see, e.g., Zanakis et al, 1984; Bongiovanni et al, 1999; Kwon et al, 2002; Hu et al, 2005; Karakozova et al, 2006; Decca et al, 2007; Rai et al, 2008; Saha and Kashina, 2011; Lee et al, 2012; Jiang et al, 2016; Wang et al, 2017a; Wang et al, 2017b) It was initially characterized as a post-translational modification of the protein N-termini for ubiquitin-proteasomal degradation (Ciechanover et al, 1988; Balzi et al, 1990). G-protein signaling is involved in virtually every known physiological process and plays a major role in neural signal transduction (Stewart and Fisher, 2015; Squires et al, 2018) It involves three crucial components: G-protein coupled receptors (GPCRs), G-protein heterotrimers, and Regulator of G-protein signaling (RGS) proteins. Opposite to GPCRs, RGS proteins accelerate the termination of G-protein signaling by facilitating hydrolysis of the GTP bound to the Gα subunit of the G-protein, and promoting its re-association with Gβγ subunits and GPCRs (De Vries et al, 1995; Dohlman et al, 1995; Druey et al, 1996; Hunt et al, 1996; Koelle and Horvitz, 1996; Watson et al, 1996)

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