Linear motifs in the C-terminus of D. melanogaster cryptochrome

Hemsley, Matthew; Mazzotta, Gabriella; Mason, Moyra; Dissel, Stephane; Toppo, Stefano; Pagano, Mario A.; Sandrelli, Federica; Meggio, Flavio; Rosato, Ezio; Costa, Rodolfo; Tosatto, Silvio C. E.

doi:10.1016/j.bbrc.2007.01.189

Cited by 33 publications

(65 citation statements)

References 36 publications

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“…In fact, it has been hypothesized that the activation of dCRY by light is mediated also by specific "regulators" that bind its C terminus, known to regulate the light dependence of dCRY activity (13). This hypothesis was supported by the observation that the C terminus of dCRY is a hotspot for molecular interactions: by in silico analysis and experimental validation, we could identify several proteinprotein interaction motifs in this small region and, among them, two class III PDZ-binding motifs (3). PDZ (postsynaptic density protein 95, Drosophila disk large tumor suppressor, and zonula occludens-1 protein) domains are modular domains that play a crucial role in the assembly of large protein complexes involved in signaling processes.…”

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confidence: 75%

“…Cryptochromes are flavoproteins highly similar to photolyases, from which they have probably evolved, but across evolution they have lost or reduced the photolyase activity and gained roles in signaling (2). Cryptochromes consist of two protein domains: an N-terminal domain homologous to photolyases (Photolyase Related, or PHR), and a very divergent C-terminal tail (3). A class of cryptochromes, CRY-DASH (drosophila, arabidopsis, synechocystis, homo), with single-stranded DNA repair activity and without the C terminus tail, has been described in bacteria, plants, and animals (2).…”

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confidence: 99%

“…dCRY interacts also with the kinase shaggy/GSK3 (SGG), and the cryptochrome's stability in light is considerably increased by this interaction whereas the inactivation of the kinase leads to the degradation of dCRY in darkness (10). The molecular mechanism by which dCRY is activated by light is still not fully understood, but a regulatory role for the C terminus of the protein has been demonstrated by several studies (3,5,(11)(12)(13). The activation of dCRY by light requires a conformational change (13), but the release of a putative repressor cannot be excluded (11).…”

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confidence: 99%

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Fly cryptochrome and the visual system

Mazzotta

Rossi

Leonardi

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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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 visualsignaling 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.

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confidence: 75%

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confidence: 99%

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Fly cryptochrome and the visual system

Mazzotta

Rossi

Leonardi

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Both substitutions, at nucleotide positions 1212 and 1865, resulted in the replacement of amino acids: arginine with serine and lysine with asparagine at amino acid positions 285 and 502 in the S and L strains, respectively. One of the two amino acid substitutions, is known to be located within the carboxy-terminal side of the DM1 region (Hemsley et al, 2007). Neither of the two amino acid substitutions were at cofactor binding sites, 5, 10-methenyltetra-hydrofolate, FAD and cyclobutane pyrimidine dimer (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

“…Transformed Drosophila flies, in which the CRY (CRY1) function was genetically manipulated by overexpression of the carboxy terminus-removed CRY, showed a longer free-running period of locomotor activity than wild-type flies (Dissel et al, 2004). This carboxy terminus region consists of two parts: one is involved in direct interactions with other molecules, the other represses these interactions in a light-dependent manner (Hemsley et al, 2007). One of the two amino acid substitutions (CRY502) in B. cucurbitae, was located in the carboxy-terminal side, positioned within the former part of the carboxy terminus region.…”

Section: Discussionmentioning

confidence: 99%

The clock gene cryptochrome of Bactrocera cucurbitae (Diptera: Tephritidae) in strains with different mating times

et al. 2009

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Differences in mating time between populations can give rise to premating reproductive isolation. Tephritid fruit flies exhibit large variation in mating time among intra-or inter-specific populations. We previously cloned the clock gene period from two strains of melon fly, Bactrocera cucurbitae; in one the individuals mate early during the day, whereas in the other the individuals mate later. These strains were originally established by divergent artificial selection for developmental time, 'short' and 'long', with early and late mating times, respectively. The deduced amino acid sequences of PERI-OD proteins for these two strains were reported to be identical. Here we cloned another clock gene cryptochrome (cry) from the two strains, and found two stable amino acid substitutions in the strains. In addition, the allele frequency at the two polymorphic sites of cry gene correlated with the circadian locomotor period (t) across strains, whereas the expression pattern of cry mRNA in the heads of flies taken from the short strain significantly differed from that from the long strain. These findings suggest that variation in the cry gene is related to differences in the circadian behaviour in the two strains, thus implying that the cry gene may have an important role in reproductive isolation.

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A PDZ scaffolding/CaM‐mediated pathway in Cryptochrome signaling

Bellanda,

Damulewicz,

Zambelli

et al. 2024

Protein Science

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Cryptochromes are cardinal constituents of the circadian clock, which orchestrates daily physiological rhythms in living organisms. A growing body of evidence points to their participation in pathways that have not traditionally been associated with circadian clock regulation, implying that cryptochromes may be subject to modulation by multiple signaling mechanisms. In this study, we demonstrate that human CRY2 (hCRY2) forms a complex with the large, modular scaffolding protein known as Multi‐PDZ Domain Protein 1 (MUPP1). This interaction is facilitated by the calcium‐binding protein Calmodulin (CaM) in a calcium‐dependent manner. Our findings suggest a novel cooperative mechanism for the regulation of mammalian cryptochromes, mediated by calcium ions (Ca2+) and CaM. We propose that this Ca2+/CaM‐mediated signaling pathway may be an evolutionarily conserved mechanism that has been maintained from Drosophila to mammals, most likely in relation to its potential role in the broader context of cryptochrome function and regulation. Further, the understanding of cryptochrome interactions with other proteins and signaling pathways could lead to a better definition of its role within the intricate network of molecular interactions that govern circadian rhythms.

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Linear motifs in the C-terminus of D. melanogaster cryptochrome

Cited by 33 publications

References 36 publications

Fly cryptochrome and the visual system

Fly cryptochrome and the visual system

The clock gene cryptochrome of Bactrocera cucurbitae (Diptera: Tephritidae) in strains with different mating times

A PDZ scaffolding/CaM‐mediated pathway in Cryptochrome signaling

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