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• W2029507401 abstract "Arrestins belong to a family of multifunctional adaptor proteins that regulate internalization of diverse receptors including G-protein-coupled receptors (GPCRs). Defects associated with endocytosis of GPCRs have been linked to human diseases. We used enhanced green fluorescent protein-tagged arrestin 2 (Arr2) to monitor the turnover of the major rhodopsin (Rh1) in live <i>Drosophila</i>. We demonstrate that during degeneration of <i>norpA^P24</i> photoreceptors the loss of Rh1 is parallel to the disappearance of rhabdomeres, the specialized visual organelle that houses Rh1. The cause of degeneration in <i>norpA^P24</i> is the failure to activate CaMKII (Ca²⁺/calmodulin-dependent protein kinase II) and retinal degeneration C (RDGC) because of a loss of light-dependent Ca²⁺ entry. A lack of activation in CaMKII, which phosphorylates Arr2, leads to hypophosphorylated Arr2, while a lack of activation of RDGC, which dephosphorylates Rh1, results in hyperphosphorylated Rh1. We investigated how reversible phosphorylation of Rh1 and Arr2 contributes to photoreceptor degeneration. To uncover the consequence underlying a lack of CaMKII activation, we characterized <i>ala¹</i> flies in which CaMKII was suppressed by an inhibitory peptide, and showed that morphology of rhabdomeres was not affected. In contrast, we found that expression of phosphorylation-deficient Rh1s, which either lack the C terminus or contain Ala substitution in the phosphorylation sites, was able to prevent degeneration of <i>norpA^P24</i> photoreceptors. This suppression is not due to a loss of Arr2 interaction. Importantly, co-expression of these modified Rh1s offered protective effects, which greatly delayed photoreceptor degeneration. Together, we conclude that phosphorylation of Rh1 is the major determinant that orchestrates its internalization leading to retinal degeneration." @default.
• W2029507401 created "2016-06-24" @default.
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• W2029507401 date "2012-08-01" @default.
• W2029507401 modified "2023-10-16" @default.
• W2029507401 title "Role of Rhodopsin and Arrestin Phosphorylation in Retinal Degeneration of Drosophila" @default.
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• W2029507401 doi "https://doi.org/10.1523/jneurosci.0565-12.2012" @default.
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