Arginylation affects G-protein signaling and visual processing in the retina

Abstract

Arginylation is a posttranslational modification that has been recently implicated in multiple key processes in development and physiology. Here we studied the effect of the neuron-specific knockout of arginyltransferase (Ate1) on visual processing in the retina using a conditional knockout model with Ate1 deletion driven by brain-specific Nestin (Nes) promoter. Electroretinography studies showed a thirty percent increase of the response of the dark-adapted retina bipolar neurons to dim light flashes in Nes-Ate1 mice compared to age-matched controls. Immunohistochemistry of retina sections showed an increase in one of the regulators of G-protein signaling (RGS) in Ate1 knockout, likely due to inhibition of its arginylation-dependent degradation by the N-end rule pathway. Since the dim-light responses in bipolar neurons are facilitated by RGSs accelerating G-proteins' GTP hydrolysis rates, increased RGS protein levels leads to increased dim-light responses. Our data suggest that Ate1-mediated arginylation affects G-protein signaling in the retina by regulating RGS proteins, facilitating the proper balance of RGS family members in the healthy retina, and ensuring normal processing of visual stimuli in the healthy animals. Supported by NIH/NEI P30 EY001583, NIH/NIGMS R01 GM104003 and R01 GM108744, and University Research Foundation, University of Pennsylvania