{"doi":"10.1523/jneurosci.2122-08.2008","title":"Mutation of a TADR Protein Leads to Rhodopsin and G<sub>q</sub>-Dependent Retinal Degeneration in<i>Drosophila</i>","abstract":"<jats:p>The<jats:italic>Drosophila</jats:italic>photoreceptor is a model system for genetic study of retinal degeneration. Many gene mutations cause fly photoreceptor degeneration, either because of excessive stimulation of the visual transduction (phototransduction) cascade, or through apoptotic pathways that in many cases involve a visual arrestin Arr2. Here we report a gene named<jats:italic>tadr</jats:italic>(for<jats:italic>t</jats:italic>orn<jats:italic>a</jats:italic>nd<jats:italic>d</jats:italic>iminished<jats:italic>r</jats:italic>habdomeres), which, when mutated, leads to photoreceptor degeneration through a different mechanism. Degeneration in the<jats:italic>tadr</jats:italic>mutant is characterized by shrunk and disrupted rhabdomeres, the light sensory organelles of photoreceptor. The TADR protein interacted<jats:italic>in vitro</jats:italic>with the major light receptor Rh1 rhodopsin, and genetic reduction of the Rh1 level suppressed the<jats:italic>tadr</jats:italic>mutation-caused degeneration, suggesting the degeneration is Rh1-dependent. Nonetheless, removal of phospholipase C (PLC), a key enzyme in phototransduction, and that of Arr2 failed to inhibit rhabdomeral degeneration in the<jats:italic>tadr</jats:italic>mutant background. Biochemical analyses revealed that, in the<jats:italic>tadr</jats:italic>mutant, the G<jats:sub>q</jats:sub>protein of Rh1 is defective in dissociation from the membrane during light stimulation. Importantly, reduction of G<jats:sub>q</jats:sub>level by introducing a hypomorphic allele of<jats:italic>G</jats:italic><jats:sub>α<jats:italic>q</jats:italic></jats:sub>gene greatly inhibited the<jats:italic>tadr</jats:italic>degeneration phenotype. These results may suggest that loss of a potential TADR-Rh1 interaction leads to an abnormality in the G<jats:sub>q</jats:sub>signaling, which in turn triggers rhabdomeral degeneration independent of the PLC phototransduction cascade. We propose that TADR-like proteins may also protect photoreceptors from degeneration in mammals including humans.</jats:p>","journal":"The Journal of Neuroscience","year":2008,"id":649519,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1173690,"name":"Peiyi Guo","orcid":null,"position":1,"is_corresponding":false},{"id":394303,"name":"Keith Reddig","orcid":null,"position":2,"is_corresponding":false},{"id":1693255,"name":"Mirna Mitra","orcid":null,"position":3,"is_corresponding":false},{"id":1693256,"name":"Hong-Sheng Li","orcid":null,"position":4,"is_corresponding":false},{"id":636948,"name":"Lina Ni","orcid":"0000-0003-2155-5155","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Mutation of a TADR Protein Leads to Rhodopsin and G<sub>q</sub>-Dependent Retinal Degeneration in<i>Drosophila</i>","abstract":"<jats:p>The<jats:italic>Drosophila</jats:italic>photoreceptor is a model system for genetic study of retinal degeneration. Many gene mutations cause fly photoreceptor degeneration, either because of excessive stimulation of the visual transduction (phototransduction) cascade, or through apoptotic pathways that in many cases involve a visual arrestin Arr2. Here we report a gene named<jats:italic>tadr</jats:italic>(for<jats:italic>t</jats:italic>orn<jats:italic>a</jats:italic>nd<jats:italic>d</jats:italic>iminished<jats:italic>r</jats:italic>habdomeres), which, when mutated, leads to photoreceptor degeneration through a different mechanism. Degeneration in the<jats:italic>tadr</jats:italic>mutant is characterized by shrunk and disrupted rhabdomeres, the light sensory organelles of photoreceptor. The TADR protein interacted<jats:italic>in vitro</jats:italic>with the major light receptor Rh1 rhodopsin, and genetic reduction of the Rh1 level suppressed the<jats:italic>tadr</jats:italic>mutation-caused degeneration, suggesting the degeneration is Rh1-dependent. Nonetheless, removal of phospholipase C (PLC), a key enzyme in phototransduction, and that of Arr2 failed to inhibit rhabdomeral degeneration in the<jats:italic>tadr</jats:italic>mutant background. Biochemical analyses revealed that, in the<jats:italic>tadr</jats:italic>mutant, the G<jats:sub>q</jats:sub>protein of Rh1 is defective in dissociation from the membrane during light stimulation. Importantly, reduction of G<jats:sub>q</jats:sub>level by introducing a hypomorphic allele of<jats:italic>G</jats:italic><jats:sub>α<jats:italic>q</jats:italic></jats:sub>gene greatly inhibited the<jats:italic>tadr</jats:italic>degeneration phenotype. These results may suggest that loss of a potential TADR-Rh1 interaction leads to an abnormality in the G<jats:sub>q</jats:sub>signaling, which in turn triggers rhabdomeral degeneration independent of the PLC phototransduction cascade. We propose that TADR-like proteins may also protect photoreceptors from degeneration in mammals including humans.</jats:p>","is_dataset_classified":null,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19074021","pmcid":"PMC2630459","openalex_id":"https://openalex.org/W1997713949","authors":[],"funders":[{"funder_name":"NIA NIH HHS","grant_id":"R01-AG022508","title":null},{"funder_name":"NIA NIH HHS","grant_id":"R01 AG022508","title":null}],"total_grants":2,"fwci":0.3903,"citation_percentile":0.60734463,"influential_citations":0,"citation_trend":[{"year":2013,"count":1},{"year":2014,"count":1},{"year":2016,"count":1},{"year":2021,"count":1},{"year":2022,"count":1}],"oa_status":"bronze","license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","oa_locations":[{"url":"https://www.jneurosci.org/content/jneuro/28/50/13478.full.pdf","host_type":"journal"},{"url":"https://www.jneurosci.org/content/jneuro/28/50/13478.full.pdf","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1523/JNEUROSCI.2122-08.2008","host_type":"publisher"},{"url":"https://doi.org/10.1523/jneurosci.2122-08.2008","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/19074021","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2630459","host_type":"repository"}],"fields_of_study":["Retinal Development and Disorders","Photoreceptor and optogenetics research","Neuroscience and Neuropharmacology Research"],"mesh_terms":["Animals","Drosophila","Electroretinography","Mutation","Retinal Degeneration","Rhodopsin","Genes, Insect","Photoreceptor Cells, Invertebrate","Patch-Clamp Techniques","Reverse Transcriptase Polymerase Chain Reaction","Drosophila Proteins","GTP-Binding Protein alpha Subunits, Gq-G11","Microscopy, Electron, Transmission"],"keywords":["Visual phototransduction","Retinal degeneration","Rhodopsin","Biology","Cell biology","Retinitis pigmentosa","Arrestin","Degeneration (medical)","Mutant","Retina","Signal transduction","Genetics","Retinal","Gene","Neuroscience","Biochemistry","G protein-coupled receptor"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T03:51:01.357767Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}