Light intensity-dependent arrestin switching for inactivation of a light-sensitive GPCR, bistable opsin

Inactivation of most light-sensitive G protein-coupled receptor (GPCR) opsins involves arrestin binding to terminate cell responses. In the zebrafish pineal organ, UV sensitive parapinopsin 1 (PP1)-expressing cells exhibit color opponency through photoequilibria between two photo-interconvertible states of PP1. The amount of visible light-sensitive active states (photoproducts) is crucial for generating color opponency, raising questions about how and what arrestins are involved in PP1 inactivation. Here, we found two arrestins, Arr3a and Sagb competitively bind to PP1. Photoresponse analyses of the PP1 cells using gene-knockdown larvae revealed Arr3a-involved quick inactivation was switched to Sagb-involved moderate inactivation depending on increased light intensity. Furthermore, we found photoregeneration of PP1 facilitates the dissociation of the PP1-arrestin complex, allowing for continuous arrestin supply in the photoequilibria under strong light. These regulations for the active photoproduct amounts of PP1 may help maintain appropriate color opponency. The current findings provide insight into the dynamics of GPCR inactivation involving multiple arrestins.