The Formation of Stable Rhodopsin-Arrestin Complexes Induces Apoptosis and Photoreceptor Cell Degeneration

Alloway, Paul G.; Howard, Louisa; Dolph, Patrick J.

doi:10.1016/s0896-6273(00)00091-x

Cited by 217 publications

(265 citation statements)

References 49 publications

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“…Despite the diversity in mechanisms underlying photoreceptor cell death in Drosophila, many of the retinal degenerations show features of apoptosis, which is reminiscent of human retinal dystrophies [31,98,234,235]. Although a lot of progress has been made over the past few years, there remain many unanswered questions regarding the mechanisms of retinal degeneration in Drosophila.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, Arr1 may also participate in deactivation since termination is more severe when both arr1 and arr2 are mutated [95]. Unlike the case with the vertebrate rhodopsins, the binding of Arr2 to Rh1 is not dependent on phosphorylation of Rh1 [96][97][98]. However, phosphorylation of the C terminus of rhodopsin contributes to Arr1 binding and this interaction promotes endocytosis of Rh1, which is proposed to play a role in scavenging spontaneously activated, phosphorylated metarhodopsin [99].…”

Section: The Rhodopsin Cycle In Drosophilamentioning

confidence: 99%

“…Endocytosis of stable Rh1/Arr2 complexes leads to retinal degeneration It appears that during and after light exposure, a small proportion of the rhodopsin pool is removed from the rhabdomeral membrane and degraded, possibly as a quality control mechanism to dispose of photodamaged or constitutively active rhodopsin [98]. Abnormal increases or decreases in the rhodopsin turnover pathway appear to cause retinal degeneration.…”

Section: Retinal Degenerationmentioning

confidence: 99%

See 2 more Smart Citations

Phototransduction and retinal degeneration in Drosophila

Wang

Montell

2007

Pflugers Arch - Eur J Physiol

258

303

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Drosophila visual transduction is the fastest known G-protein-coupled signaling cascade and has therefore served as a genetically tractable animal model for characterizing rapid responses to sensory stimulation. Mutations in over 30 genes have been identified, which affect activation, adaptation, or termination of the photoresponse. Based on analyses of these genes, a model for phototransduction has emerged, which involves phosphoinoside signaling and culminates with opening of the TRP and TRPL cation channels. Many of the proteins that function in phototransduction are coupled to the PDZ containing scaffold protein INAD and form a supramolecular signaling complex, the signalplex. Arrestin, TRPL, and Gα q undergo dynamic light-dependent trafficking, and these movements function in long-term adaptation. Other proteins play important roles either in the formation or maturation of rhodopsin, or in regeneration of phosphatidylinositol 4,5-bisphosphate (PIP 2 ), which is required for the photoresponse. Mutation of nearly any gene that functions in the photoresponse results in retinal degeneration. The underlying bases of photoreceptor cell death are diverse and involve mechanisms such as excessive endocytosis of rhodopsin due to stable rhodopsin/arrestin complexes and abnormally low or high levels of Ca 2+ . Drosophila visual transduction appears to have particular relevance to the cascade in the intrinsically photosensitive retinal ganglion cells in mammals, as the photoresponse in these latter cells appears to operate through a remarkably similar mechanism.

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Section: Discussionmentioning

confidence: 99%

Section: The Rhodopsin Cycle In Drosophilamentioning

confidence: 99%

Section: Retinal Degenerationmentioning

confidence: 99%

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Phototransduction and retinal degeneration in Drosophila

Wang

Montell

2007

Pflugers Arch - Eur J Physiol

258

303

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“…They also facilitate the endocytic turnover of light-activated Rhodopsin. In Arrestin mutants, the photoreceptors degenerate because of endocytic defects [58][59][60]. In these mutants, chronically active rhodopsin leads to increased calcium entry, calcium necrotoxicity, and the defective endocytosis of rhodopsin.…”

Section: Sphingolipids In Endocytosis and Exocytosismentioning

confidence: 99%

Sphingolipids and membrane biology as determined from genetic models

Rao

Acharya

2008

Prostaglandins & Other Lipid Mediators

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The importance of sphingolipids in membrane biology was appreciated early in the twentieth century when several human inborn errors of metabolism were linked to defects in sphingolipid degradation. The past two decades have seen an explosion of information linking sphingolipids with cellular processes. Studies have unraveled mechanistic details of the sphingolipid metabolic pathways, and these findings are being exploited in the development of novel therapies, some now in clinical trials. Pioneering work in yeast has laid the foundation for identifying genes encoding the enzymes of the pathways. The advent of the era of genomics and bioinformatics has led to the identification of homologous genes in other species and the subsequent creation of animal knock-out lines for these genes. Discoveries from these efforts have re-kindled interest in the role of sphingolipids in membrane biology. This review highlights some of the recent advances in understanding sphingolipids' roles in membrane biology as determined from genetic models.

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“…Arr2 is phosphorylated by calcium/calmodulin-dependent kinase II (CamKII) (Matsumoto et al, 1994;Yamada et al, 1990), which is activated by Ca 2+ influx through the light activated TRP and TRPL channels (Alloway and Dolph, 1999;Byk et al, 1993;Kiselev et al, 2000;Peretz et al, 1994). Mutations which cause stable association between Arr2 and metarhodopsin result in clathrin-dependent endocytosis of the metarhodopsin-Arr2 complexes into the cell body that eventually lead to degeneration of the photoreceptor cell (Alloway and Dolph, 1999;Alloway et al, 2000;Kiselev et al, 2000;Orem and Dolph, 2002).…”

Section: Light Adaptation Through Phosphoinositide and Ninac Myosin Imentioning

confidence: 99%

Light-regulated translocation of signaling proteins in Drosophila photoreceptors

Frechter

Minke

2006

Journal of Physiology-Paris

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Illumination of Drosophila photoreceptor cells induces multi-facet responses, which include generation of the photoreceptor potential, screening pigment migration and translocation of signaling proteins which is the focus of recent extensive research. Translocation of three signaling molecules is covered in this review: (1) Light-dependent translocation of arrestin from the cytosol to the signaling membrane, the rhabdomere, determines the lifetime of activated rhodopsin. Arrestin translocates in PIP 3 and NINAC myosin III dependent manner, and specific mutations which disrupt the interaction between arrestin and PIP 3 or NINAC also impair the light-dependant translocation of arrestin and the termination of the response to light. (2) Activation of Drosophila visual G protein, DGq, causes a massive and reversible, translocation of the α subunit from the signaling membrane to the cytosol, accompanied by activity-dependent architectural changes. Analysis of the translocation and the recovery kinetics of DGq α in wild-type flies and specific visual mutants indicated that DGq α is necessary but not sufficient for the architectural changes. (3) The TRP-like (TRPL) but not TRP channels translocate in a light-dependent manner between the rhabdomere and the cell body. As a physiological consequence of this light-dependent modulation of the TRP/TRPL ratio, the photoreceptors of dark-adapted flies operate at a wider dynamic range, which allows the photoreceptors enriched with TRPL to function better in darkness and dim background illumination. Altogether, signal-dependent movement of signaling proteins plays a major role in the maintenance and function of photoreceptor cells.

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The Formation of Stable Rhodopsin-Arrestin Complexes Induces Apoptosis and Photoreceptor Cell Degeneration

Cited by 217 publications

References 49 publications

Phototransduction and retinal degeneration in Drosophila

Phototransduction and retinal degeneration in Drosophila

Sphingolipids and membrane biology as determined from genetic models

Light-regulated translocation of signaling proteins in Drosophila photoreceptors

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