title: Role of Ca2+/calmodulin-dependent protein kinase II in Drosophila photoreceptors.
abstract: Ca(2+) modulates the visual response in both vertebrates and invertebrates. In Drosophila photoreceptors, an increase of cytoplasmic Ca(2+) mimics light adaptation. Little is known regarding the mechanism, however. We explored the role of the sole Drosophila Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) to mediate light adaptation. CaMKII has been implicated in the phosphorylation of arrestin 2 (Arr2). However, the functional significance of Arr2 phosphorylation remains debatable. We identified retinal CaMKII by anti-CaMKII antibodies and by its Ca(2+)-dependent autophosphorylation. Moreover, we show that phosphorylation of CaMKII is greatly enhanced by okadaic acid, and indeed, purified PP2A catalyzes the dephosphorylation of CaMKII. Significantly, we demonstrate that anti-CaMKII antibodies co-immunoprecipitate, and CaMKII fusion proteins pull down the catalytic subunit of PP2A from fly extracts, indicating that PP2A interacts with CaMKII to form a protein complex. To investigate the function of CaMKII in photoreceptors, we show that suppression of CaMKII in transgenic flies affects light adaptation and increases prolonged depolarizing afterpotential amplitude, whereas a reduced PP2A activity brings about reduced prolonged depolarizing afterpotential amplitude. Taken together, we conclude that CaMKII is involved in the negative regulation of the visual response affecting light adaptation, possibly by catalyzing phosphorylation of Arr2. Moreover, the CaMKII activity appears tightly regulated by the co-localized PP2A.
authors.affiliation: Department of Pharmacology, Center for Molecular Neuroscience, and Vision Research Center, Vanderbilt University, Nashville, Tennessee 37232, USA.
authors.forename: Haiqin
authors.initials: H
authors.lastname: Lu
authors.forename: Hung-Tat
authors.initials: HT
authors.lastname: Leung
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: William L
authors.initials: WL
authors.lastname: Pak
authors.forename: Bih-Hwa
authors.initials: BH
authors.lastname: Shieh
mesh_terms: D000818:Animals; D019390:Arrestins / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism / Q000502:physiology*; D002147:Calmodulin / Q000737:chemistry; D002384:Catalysis; D020134:Catalytic Domain; D003600:Cytosol / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D004596:Electroretinography / Q000379:methods; D006579:Heterozygote; D010641:Phenotype; D010766:Phosphorylation; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: C504666:Arr2 protein, Drosophila; D019390:Arrestins; D002147:Calmodulin; D029721:Drosophila Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium