Light intensity-dependent arrestin switching for inactivation of a light-sensitive GPCR, bistable opsin
Baoguo Shen1,2, Seiji Wada1,2,3, Tomohiro Sugihara1,2
1Department of Biology, Graduate School of Science, Osaka Metropolitan University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan.
Abstract:
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.
Insights
Zebrafish use two arrestins, Arr3a and Sagb, to control light sensitivity in pineal cells. Their switching mechanism ensures proper color vision under varying light conditions.
Area of Science:
- * Neuroscience
- * Molecular Biology
- * Vision Research
Background:
- * Light-sensitive G protein-coupled receptor (GPCR) opsins are typically inactivated by arrestin binding, which terminates cellular responses.
- * In zebrafish, UV-sensitive parapinopsin 1 (PP1) in pineal cells generates color opponency via photoequilibria between two states.
- * The quantity of active PP1 states is critical for color opponency, necessitating an understanding of arrestin involvement in PP1 inactivation.
Purpose of the Study:
- * To investigate the specific arrestins involved in the inactivation of zebrafish parapinopsin 1 (PP1).
- * To elucidate how light intensity influences the arrestin-mediated inactivation of PP1.
- * To explore the role of PP1 photoregeneration in regulating arrestin binding and maintaining color opponency.
Main Methods:
- * Photoresponse analyses were conducted on PP1-expressing cells in gene-knockdown zebrafish larvae.
- * Competitive binding assays were used to identify arrestins interacting with PP1.
- * Investigated the effect of PP1 photoregeneration on PP1-arrestin complex dynamics.
Main Results:
- * Identified Arr3a and Sagb as arrestins that competitively bind to PP1.
- * Observed a light-dependent switch in inactivation: Arr3a mediates rapid inactivation at lower light, while Sagb mediates moderate inactivation at higher light intensities.
- * Demonstrated that PP1 photoregeneration promotes the dissociation of PP1-arrestin complexes, enabling sustained arrestin availability under strong light.
Conclusions:
- * Zebrafish utilize a dual arrestin system (Arr3a and Sagb) for dynamic regulation of PP1 inactivation.
- * Light intensity dictates which arrestin dominates PP1 inactivation, fine-tuning cellular responses.
- * Photoregeneration of PP1 is a key mechanism for maintaining continuous arrestin supply and appropriate color opponency under varying light conditions.
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