Phototransduction and retinal degeneration in Drosophila.
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 G alpha(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 (PIP2), 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 Ca2+. 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.
Wang
Tao
T
Department of Biological Chemistry, Center for Sensory Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Montell
Craig
C
D000221:Adaptation, Ocular / Q000502:physiology / Q000528:radiation effects; D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D004330:Drosophila / Q000033:anatomy & histology / Q000502:physiology*; D029721:Drosophila Proteins / Q000502:physiology / Q000528:radiation effects; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology; D017344:Genes, Insect / Q000502:physiology; D008027:Light; D046912:Multiprotein Complexes / Q000502:physiology; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D017956:Photoreceptor Cells, Invertebrate / Q000033:anatomy & histology / Q000473:pathology / Q000502:physiology*; D012162:Retinal Degeneration; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D050051:Transient Receptor Potential Channels / Q000502:physiology; D014785:Vision, Ocular / Q000502:physiology* / Q000528:radiation effects; D014801:Vitamin A / Q000096:biosynthesis
D015220:Calcium Channels; D029721:Drosophila Proteins; D005136:Eye Proteins; D046912:Multiprotein Complexes; D019269:Phosphatidylinositol 4,5-Diphosphate; D050051:Transient Receptor Potential Channels; C074192:trpl protein, Drosophila; D014801:Vitamin A; D012243:Rhodopsin; D019204:GTP-Binding Proteins