title: Fly cryptochrome and the visual system.
abstract: Cryptochromes are flavoproteins, structurally and evolutionarily related to photolyases, that are involved in the development, magnetoreception, and temporal organization of a variety of organisms. Drosophila CRYPTOCHROME (dCRY) is involved in light synchronization of the master circadian clock, and its C terminus plays an important role in modulating light sensitivity and activity of the protein. The activation of dCRY by light requires a conformational change, but it has been suggested that activation could be mediated also by specific "regulators" that bind the C terminus of the protein. This C-terminal region harbors several protein-protein interaction motifs, likely relevant for signal transduction regulation. Here, we show that some functional linear motifs are evolutionarily conserved in the C terminus of cryptochromes and that class III PDZ-binding sites are selectively maintained in animals. A coimmunoprecipitation assay followed by mass spectrometry analysis revealed that dCRY interacts with Retinal Degeneration A (RDGA) and with Neither Inactivation Nor Afterpotential C (NINAC) proteins. Both proteins belong to a multiprotein complex (the Signalplex) that includes visual-signaling molecules. Using bioinformatic and molecular approaches, dCRY was found to interact with Neither Inactivation Nor Afterpotential C through Inactivation No Afterpotential D (INAD) in a light-dependent manner and that the CRY-Inactivation No Afterpotential D interaction is mediated by specific domains of the two proteins and involves the CRY C terminus. Moreover, an impairment of the visual behavior was observed in fly mutants for dCRY, indicative of a role, direct or indirect, for this photoreceptor in fly vision.
authors.affiliation: Department of Biology, University of Padova, 35131 Padova, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Mazzotta
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rossi
authors.forename: Emanuela
authors.initials: E
authors.lastname: Leonardi
authors.forename: Moyra
authors.initials: M
authors.lastname: Mason
authors.forename: Cristiano
authors.initials: C
authors.lastname: Bertolucci
authors.forename: Laura
authors.initials: L
authors.lastname: Caccin
authors.forename: Barbara
authors.initials: B
authors.lastname: Spolaore
authors.forename: Alberto J M
authors.initials: AJ
authors.lastname: Martin
authors.forename: Matthias
authors.initials: M
authors.lastname: Schlichting
authors.forename: Rudi
authors.initials: R
authors.lastname: Grebler
authors.forename: Charlotte
authors.initials: C
authors.lastname: Helfrich-Förster
authors.forename: Stefano
authors.initials: S
authors.lastname: Mammi
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Costa
authors.forename: Silvio C E
authors.initials: SC
authors.lastname: Tosatto
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D019295:Computational Biology; D056931:Cryptochromes / Q000502:physiology*; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster / Q000378:metabolism / Q000502:physiology*; D004596:Electroretinography; D005136:Eye Proteins / Q000502:physiology*; D005420:Flavoproteins / Q000378:metabolism; D008027:Light; D013058:Mass Spectrometry; D025941:Protein Interaction Mapping; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques; D014785:Vision, Ocular / Q000502:physiology*
chemical_list: D056931:Cryptochromes; D029721:Drosophila Proteins; D005136:Eye Proteins; D005420:Flavoproteins; C119828:cry protein, Drosophila
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