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Rossi, Alessandro (2013) Fly Cryptochrome and the Visual System. [Tesi di dottorato]

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Abstract (inglese)

Cryptochromes are flavoproteins, structurally and evolutionarily related to photolyases, involved in development, magnetoreception and temporal organization of a variety of organisms. Drosophila cryptochrome (dCRY) mediates light synchronization of the master circadian clock, and is an integral component of circadian clocks in fly's peripheral tissues, where it works as a transcriptional repressor. The C-terminus of dCRY 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 it could be mediated also by specific “regulators” that bind the C- terminus of the protein. This region harbors several protein-protein interaction motifs, likely relevant for the regulation of signal transduction.
Linear motifs (LMs) are short sequences (4-5 amino acidic residues long) evolved to mediate molecular (protein-protein) interactions. Often, LMs are present in disordered non-globular protein regions with a particular preference for protein C-terminus localization. LMs have the tendency to be unstable over long evolutionary distances and, within distinct non-globular regions, it can be hypothesized that they might evolve by “jumping” between different sequence positions. Some functional linear motifs are evolutionarily conserved in the C-terminus of cryptochromes and, specifically, class III PDZ binding sites are selectively maintained in animals. A co-immunoprecipitation assay followed by mass spectrometry analysis has revealed that dCRY interacts with Retinal DeGeneration A (RDGA) and Neither Inactivation Nor Afterpotential C (NINAC). Both proteins belong to a multi-protein complex (the Signalplex) that includes visual signaling molecules. In this work, using bioinformatic and molecular approaches, it has been found that dCRY interacts with proteins of the visual cascade through INAD (Inactivation No Afterpotential D) and that the CRY-INAD interaction, mediated by specific domains of the two proteins, is light-dependent. Moreover, an impairment of the visual behavior in flies mutants for dCRY was detected, indicating a role, direct or indirect, for this photoreceptor in fly vision

Abstract (italiano)

I criptocromi sono flavoproteine, strutturalmente ed evolutivamente legate alle fotoliasi, coinvolte nello sviluppo, magnetorecezione e organizzazione temporale di una varietà di organismi. Il criptocromo di Drosofila (dCRY) media la sincronizzazione luminosa dell’orologio circadiano principale ed inoltre è un componente fondamentale degli orologi circadiani nei tessuti periferici dell’insetto dove agisce come repressore trascrizionale.
Il C-terminale di dCRY ha un ruolo importante nel modulare la sensibilità alla luce e l’attività della proteina. L’attivazione di dCRY attraverso la luce richiede un cambiamento conformazionale, ma è stato ipotizzato che può essere mediata anche da specifici “regolatori” che si legano al suo C-terminale. Questa regione contiene diversi domini di interazione proteina-proteina probabilmente rilevanti per la regolazione della trasduzione del segnale. Alcuni motivi lineari sono evolutivamente conservati nel C- terminale dei criptocromi e siti di legame per i motivi PDZ di classe III sono particolarmente conservati negli animali. Esperimenti di co-immunoprecipitazione seguiti da analisi di spettrometria di massa hanno mostrato che dCRY interagisce con due proteine: Retinal DeGeneration A (RDGA) e Neither Inactivation Nor Afterpotential C (NINAC). Entrambe queste proteine appartengono ad un complesso multipeptidico (il Signalplex) che include anche molecole della cascata visiva. In questo lavoro, utilizzando un approccio sia bioinformatico che molecolare si è scoperto che dCRY interagisce con le proteine della cascata visiva attraverso Inactivation No Afterpotential D (INAD) e che l’interazione dCRY-INAD, mediata da specifici domini nelle due proteine, è luce dipendente. Si è osservato che esiste un impedimento visivo nelle mosche mutanti per dCRY, il che indica un ruolo, diretto od indiretto, di questo fotorecettore nella visione delle mosche

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Tipo di EPrint:Tesi di dottorato
Relatore:Stefano, Mammi
Dottorato (corsi e scuole):Ciclo 25 > Scuole 25 > BIOSCIENZE E BIOTECNOLOGIE > BIOTECNOLOGIE
Data di deposito della tesi:22 Gennaio 2013
Anno di Pubblicazione:31 Gennaio 2013
Parole chiave (italiano / inglese):Drosophila PDZ domains INAD CRYPTOCHROME
Settori scientifico-disciplinari MIUR:Area 05 - Scienze biologiche > BIO/11 Biologia molecolare
Struttura di riferimento:Dipartimenti > Dipartimento di Scienze Chimiche
Codice ID:5413
Depositato il:10 Ott 2013 14:31
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