Dissecting independent channel and scaffolding roles of the Drosophila transient receptor potential channel.
Drosophila transient receptor potential (TRP) serves dual roles as a cation channel and as a molecular anchor for the PDZ protein, INAD (inactivation no afterpotential D). Null mutations in trp cause impairment of visual transduction, mislocalization of INAD, and retinal degeneration. However, the impact of specifically altering TRP channel function is not known because existing loss-of-function alleles greatly reduce protein expression. In the current study we describe the isolation of a set of new trp alleles, including trp(14) with an amino acid substitution juxtaposed to the TRP domain. The trp(14) flies stably express TRP and display normal molecular anchoring, but defective channel function. Elimination of the anchoring function alone in trp(Delta)(1272), had minor effects on retinal morphology whereas disruption of channel function caused profound light-induced cell death. This retinal degeneration was greatly suppressed by elimination of the Na(+)/Ca(2+) exchanger, CalX, indicating that the cell death was due primarily to deficient Ca(2+) entry rather than disruption of the TRP-anchoring function.
Wang
Tao
T
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Jiao
Yuchen
Y
Montell
Craig
C
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017920:Antiporters / Q000235:genetics / Q000502:physiology*; D019390:Arrestins / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002412:Cations; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster; D004596:Electroretinography; D005786:Gene Expression Regulation; D017344:Genes, Insect; D047468:Immunoprecipitation; D008027:Light; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D017956:Photoreceptor Cells, Invertebrate / Q000473:pathology*; D017434:Protein Structure, Tertiary; D012160:Retina / Q000473:pathology; D012164:Retinal Diseases / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D019831:Sodium-Calcium Exchanger / Q000737:chemistry; D013997:Time Factors; D050051:Transient Receptor Potential Channels / Q000378:metabolism / Q000502:physiology*; D014785:Vision, Ocular
D017920:Antiporters; C504666:Arr2 protein, Drosophila; D019390:Arrestins; C108396:Calx protein, Drosophila; D002412:Cations; D029721:Drosophila Proteins; D019831:Sodium-Calcium Exchanger; D050051:Transient Receptor Potential Channels; C063169:trp protein, Drosophila; D002118:Calcium