Phototransduction and retinal degeneration in Drosophila

Wang, Tao; Montell, Craig

doi:10.1007/s00424-007-0251-1

Cited by 256 publications

(308 citation statements)

References 243 publications

(422 reference statements)

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“…1A shows the distribution of interactors for dCRY. The results showed a weak connection to No Receptor Potential A (NORPA), a protein belonging to the phototransduction complex (20).…”

Section: Resultsmentioning

confidence: 99%

“…Analysis of the MS/MS data using the MASCOT software yielded the identification of two proteins involved in the fly visual-signaling pathway: Retinal DeGeneration A (RDGA) in the dark and Neither Inactivation Nor Afterpotential C (NINAC) after 15 min of light pulse ( Fig. S2A) (18,20). Although RDGA was identified on the basis of the MS/ MS spectra of six different tryptic peptides, in the case of NINAC, the identification was based on the MS/MS spectrum of only one peptide displaying a significant score in MASCOT (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…S2C). Many of the elements of this visual cascade are assembled in a multiprotein-signaling complex (Signalplex) organized by INAD, a scaffold protein with five structural PDZ domains, each of which binds to a specific partner (20). A schematic representation of the functional domains of NINAC, RDGA, NORPA, and dCRY is given in Fig.…”

Section: Resultsmentioning

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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“…1A shows the distribution of interactors for dCRY. The results showed a weak connection to No Receptor Potential A (NORPA), a protein belonging to the phototransduction complex (20).…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

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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“…As mentioned previously, MPZ-1 is most homologous to INAD proteins, which in Drosophila organizes phototransduction signaling complexes containing many different components including rhodopsin, phospholipase C, transient receptor potential (TRP) channel, TRP-like channel, protein kinase C, myoIII, and calmodulin (40,46). Although we have shown that MPZ-1 interacts with ARR-1 and DAF-18, previous studies have shown that MPZ-1 also functions to regulate the serotonin receptor SER-1 in C. elegans (37).…”

Section: Discussionmentioning

confidence: 95%

Arrestin and the Multi-PDZ Domain-containing Protein MPZ-1 Interact with Phosphatase and Tensin Homolog (PTEN) and Regulate Caenorhabditis elegans Longevity

Palmitessa

Benovic

2010

Journal of Biological Chemistry

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Arrestins are multifunctional adaptor proteins best known for their role in regulating G protein-coupled receptor signaling. Arrestins also regulate other types of receptors, including the insulin-like growth factor receptor (IGF-1R), although the mechanism by which this occurs is not well understood. In Caenorhabditis elegans, the IGF-1R ortholog DAF-2 regulates dauer formation, stress resistance, metabolism, and lifespan through a conserved signaling cascade. To further elucidate the role of arrestin in IGF-1R signaling, we employed an in vivo approach to investigate the role of ARR-1, the sole arrestin ortholog in C. elegans, on longevity. Here, we report that ARR-1 functions to positively regulate DAF-2 signaling in C. elegans. arr-1 mutant animals exhibit increased longevity and enhanced nuclear localization of DAF-16, an indication of decreased DAF-2 signaling, whereas animals overexpressing ARR-1 have decreased longevity. Genetic and biochemical analysis reveal that ARR-1 functions to regulate DAF-2 signaling via direct interaction with MPZ-1, a multi-PDZ domain-containing protein, via a C-terminal PDZ binding domain in ARR-1. Interestingly, ARR-1 and MPZ-1 are found in a complex with the phosphatase and tensin homolog (PTEN) ortholog DAF-18, which normally serves as a suppressor of DAF-2 signaling, suggesting that these three proteins work together to regulate DAF-2 signaling. Our results suggest that the ARR-1-MPZ-1-DAF-18 complex functions to regulate DAF-2 signaling in vivo and provide insight into a novel mechanism by which arrestin is able to regulate IGF-1R signaling and longevity.The fundamental process of aging is regulated by a diverse number of genetic and environmental factors; however, one well established factor contributing to longevity is the insulin/ IGF-1 (IIS) 2 signaling pathway (1). Mutations that reduce IIS signaling have been demonstrated to extend lifespan in a wide range of organisms including Drosophila, Caenorhabditis elegans, mice, and humans (2, 3). For example, mutation of DAF-2, the sole insulin/IGF-1 receptor in C. elegans, doubles the normal lifespan of these animals (4, 5). The IIS signaling pathway in worms regulates longevity through a highly conserved set of components (6). Upon ligand binding, the DAF-2 receptor recruits and activates the phosphatidylinositol 3-kinase (PI3K) homolog AGE-1, resulting in the production of phosphatidylinositol 3,4,5-trisphosphate (7). This activates PDK-1, which in turn leads to activation of the serine/threonine protein kinases AKT-1, AKT-2, and SGK-1 (8 -10). These kinases phosphorylate the forkhead transcription factor DAF-16 and prevent it from entering the nucleus, an event that represses the ability of DAF-16 to regulate the transcription of genes involved in longevity (11-13). DAF-2 signaling is negatively regulated by the lipid phosphatase DAF-18, the ortholog of the human tumor suppressor PTEN (14 -16). DAF-18 catalyzes the dephosphorylation of phosphatidylinositol 3,4,5-trisphosphate, thereby antagonizing AGE-1 and disrupting t...

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“…Degeneration-In Drosophila, mutations in almost any gene involved in the phototransduction cascade lead to light-dependent retinal degeneration (34). Thus, we investigated whether the G␣ q 961 mutant and G␣ q 1 mutant also undergo retinal degeneration.…”

Section: G␣ Q 961 Mutant Undergoes Light-dependent Retinalmentioning

confidence: 99%

Protein Gq Modulates Termination of Phototransduction and Prevents Retinal Degeneration

Wan

et al. 2012

Journal of Biological Chemistry

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Background: Appropriate termination of photoresponse is critical for photoreceptors to achieve high temporal resolution and to prevent excessive Ca 2ϩ -induced cell toxicity. Results: We isolated a novel G␣ q mutant allele and revealed that metarhodopsin/G q interaction affects Arr2-Rh1 binding. Conclusion: G q modulates the termination of phototransduction and prevents retinal degeneration. Significance: Our study revealed the novel role of G q in phototransduction deactivation and in retinal degeneration.Appropriate termination of the phototransduction cascade is critical for photoreceptors to achieve high temporal resolution and to prevent excessive Ca 2؉ -induced cell toxicity. Using a genetic screen to identify defective photoresponse mutants in Drosophila, we isolated and identified a novel G␣ q mutant allele, which has defects in both activation and deactivation. We revealed that G q modulates the termination of the light response and that metarhodopsin/G q interaction affects subsequent arrestin-rhodopsin (Arr2-Rh1) binding, which mediates the deactivation of metarhodopsin. We further showed that the G␣ q mutant undergoes light-dependent retinal degeneration, which is due to the slow accumulation of stable Arr2-Rh1 complexes. Our study revealed the roles of G q in mediating photoresponse termination and in preventing retinal degeneration. This pathway may represent a general rapid feedback regulation of G protein-coupled receptor signaling.Heterotrimeric G proteins play pivotal roles in mediating extracellular signals from hormones, neurotransmitters, peptides, as well as sensory stimuli to intracellular signaling pathways (1, 2). In Drosophila photoreceptors, G proteins are essential for the activation of the phototransduction cascade (3, 4). Photon absorption leads to the photoisomerization of chromophores, resulting in the formation of activated metarhodopsin. In turn, metarhodopsin activates heterotrimeric G proteins and PLC.2 The activation of PLC leads to transient receptor potential and transient receptor potential-like channels opening and extracellular Ca 2ϩ influx (5-8). It is also critical for each step of the phototransduction cascade to be terminated appropriately, which is essential for the high temporal resolution of fly vision (9, 10). The most important step in phototransduction termination is the deactivation of metarhodopsin. During this step, arrestin (Arr2) plays an important role by displacing the G q ␣ subunit and allowing it to bind with rhodopsin (Rh1) (11,12). Unlike other G proteincoupled receptors (GPCRs), the phosphorylation of fly rhodopsin is not required for its deactivation (13) but is essential for its endocytosis (11). In contrast, the dephosphorylation of rhodopsin by retinal degeneration C (RDGC) is essential for receptor deactivation (14). Ca 2ϩ also plays critical roles in regulating the termination of the photoresponse in Drosophila (8,15,16). Several proteins that mediate this Ca 2ϩ -regulated termination have been identified, such as eye-specific protein kinase C...

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Phototransduction and retinal degeneration in Drosophila

Cited by 256 publications

References 243 publications

Fly cryptochrome and the visual system

Fly cryptochrome and the visual system

Arrestin and the Multi-PDZ Domain-containing Protein MPZ-1 Interact with Phosphatase and Tensin Homolog (PTEN) and Regulate Caenorhabditis elegans Longevity

Protein Gq Modulates Termination of Phototransduction and Prevents Retinal Degeneration

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