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 employed eGFP-tagged arrestin 2 (Arr2) to monitor the turnover of the major rhodopsin (Rh1) in live Drosophila. We demonstrate that during degeneration of norpAP24 photoreceptors the loss of Rh1 is parallel to the disappearance of rhabdomeres, the specialized visual organelle that houses Rh1. The cause of degeneration in norpAP24 is due to a failure to activate CaMKII and 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 ala1 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 norpAP24 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. Taken together, we conclude that phosphorylation of Rh1 is the major determinant that orchestrates its internalization leading to retinal degeneration.
A localized phosphate distribution (LPD) was introduced for the first time into a porous TiO 2 nanostructure by using a biotemplate synthetic strategy, that is, Staphylococcus aureus (S. aureus)-assisted in situ phosphate transfer. The resulting novel nanostructures have shown remarkable enhancement of photoactivities for both selective dye degradation and photoelectrochemical water reduction. Mechanistic understanding reveals that improved separation, directional transport, and less limited interface transfer of the photogenerated electron and hole may be achieved simultaneously within the LPD-modified TiO 2 nanostructures because of the existence of the confined negative surface electrostatic field (NSEF) and the spatially oriented upward band bending (UBB). On the contrary, a homogeneous phosphate distribution (HPD) will greatly increase electron interface transfer resistance, which will cause the increase of recombination in bulk. The most important inspiration we can obtain herein is that a comprehensive consideration of the influence of nanostructure on all of the critical aspects of the carrier's dynamics is needed during the rational design and construction of the advanced nanostructured photocatalyst systems. Considering the available resources for the synthesis and strong covalent interaction of phosphate with many other transition metal cations, the authors think that the novel strategy for a simultaneous optimization of the dynamic processes of the charge pairs by introducing LPD is promising for several applications including photocatalysis, photoelectrochemical hydrogen production, and solar cell.
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