{"doi":"10.1083/jcb.141.7.1589","title":"Structural Analysis of <i>Drosophila</i> Merlin Reveals Functional Domains Important for Growth Control and Subcellular Localization","abstract":"<jats:p>Merlin, the product of the Neurofibromatosis type 2 (NF2) tumor-suppressor gene, is a member of the protein 4.1 superfamily that is most closely related to ezrin, radixin, and moesin (ERM). NF2 is a dominantly inherited disease characterized by the formation of bilateral acoustic schwannomas and other benign tumors associated with the central nervous system. To understand its cellular functions, we are studying a Merlin homologue in Drosophila. As is the case for NF2 tumors, Drosophila cells lacking Merlin function overproliferate relative to their neighbors. Using in vitro mutagenesis, we define functional domains within Merlin required for proper subcellular localization and for genetic rescue of lethal Merlin alleles. Remarkably, the results of these experiments demonstrate that all essential genetic functions reside in the plasma membrane– associated NH2-terminal 350 amino acids of Merlin. Removal of a seven–amino acid conserved sequence within this domain results in a dominant-negative form of Merlin that is stably associated with the plasma membrane and causes overproliferation when expressed ectopically in the wing. In addition, we provide evidence that the COOH-terminal region of Merlin has a negative regulatory role, as has been shown for ERM proteins. These results provide insights into the functions and functional organization of a novel tumor suppressor gene.</jats:p>","journal":"The Journal of Cell Biology","year":1998,"id":594787,"datarank":0.7465100613630863,"base_score":4.976733742420574,"endowment":4.976733742420574,"self_citation_contribution":0.7465100613630863,"citation_network_contribution":0.0,"self_endowment_contribution":0.7465100613630863,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":144,"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":391087,"name":"Brooke M. 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As is the case for NF2 tumors, Drosophila cells lacking Merlin function overproliferate relative to their neighbors. Using in vitro mutagenesis, we define functional domains within Merlin required for proper subcellular localization and for genetic rescue of lethal Merlin alleles. Remarkably, the results of these experiments demonstrate that all essential genetic functions reside in the plasma membrane– associated NH2-terminal 350 amino acids of Merlin. Removal of a seven–amino acid conserved sequence within this domain results in a dominant-negative form of Merlin that is stably associated with the plasma membrane and causes overproliferation when expressed ectopically in the wing. In addition, we provide evidence that the COOH-terminal region of Merlin has a negative regulatory role, as has been shown for ERM proteins. These results provide insights into the functions and functional organization of a novel tumor suppressor gene.</jats:p>","is_dataset_classified":null,"base_score":4.976733742420574,"endowment":4.976733742420574,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"9647651","pmcid":"PMC2133006","openalex_id":"https://openalex.org/W2123117119","authors":[],"funders":[{"funder_name":"NINDS NIH HHS","grant_id":"R01-NS34783","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"F32 NS010224","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"R01 NS034783","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"F32-NS10224","title":null},{"funder_name":"National Institutes of Health","grant_id":"5F32NS010224-02","title":"DROSOPHILA NF2/MERLIN HOMOLOGUE"},{"funder_name":"National Institutes of Health","grant_id":"5R01NS034783-24","title":"Function of NF2/Merlin in regulation of the Hippo/Salvador/Warts growth control pathway"},{"funder_name":"National Institutes of Health","grant_id":"7R01NS034783-10","title":"Function of Merlin, a Drosophila NF2 gene homologue"}],"total_grants":7,"fwci":7.5842,"citation_percentile":0.97451415,"influential_citations":0,"citation_trend":[{"year":2012,"count":5},{"year":2013,"count":4},{"year":2014,"count":7},{"year":2015,"count":3},{"year":2016,"count":2},{"year":2017,"count":2},{"year":2018,"count":3},{"year":2019,"count":2},{"year":2020,"count":2},{"year":2021,"count":4},{"year":2022,"count":2},{"year":2023,"count":1},{"year":2024,"count":4}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://rupress.org/jcb/article-pdf/141/7/1589/1278733/9803011.pdf","host_type":"journal"},{"url":"https://rupress.org/jcb/article-pdf/141/7/1589/1278733/9803011.pdf","host_type":"publisher"},{"url":"https://rupress.org/jcb/article-pdf/141/7/1589/1492064/9803011.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1083/jcb.141.7.1589","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/9647651","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2133006","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC2133006","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC2133006?pdf=render","host_type":"Europe_PMC"},{"url":"https://dx.doi.org/10.1083/jcb.141.7.1589","host_type":""}],"fields_of_study":["Neurofibromatosis and Schwannoma Cases","Hippo pathway signaling and YAP/TAZ","Vascular Malformations Diagnosis and Treatment","0301 basic medicine","0303 health sciences","03 medical and health sciences","Animals","Binding Sites","Cell Line","Drosophila","Female","Genes, Insect","Male","Membrane Proteins","Mutagenesis","Neurofibromin 2","Recombinant Fusion Proteins","Subcellular Fractions"],"mesh_terms":["Animals","Binding Sites","Cell Line","Drosophila","Female","Male","Membrane Proteins","Recombinant Fusion Proteins","Subcellular Fractions","Mutagenesis","Genes, Insect","Neurofibromin 2"],"keywords":["Merlin (protein)","Moesin","Biology","Radixin","Ezrin","Genetics","Subcellular localization","Gene","Suppressor","Neurofibromatosis type 2","Cell biology","Phenotype","Neurofibromatosis","Cell","Cytoskeleton","Male","Neurofibromin 2","Binding Sites","Recombinant Fusion Proteins","Membrane Proteins","Genes, Insect","Cell Line","Mutagenesis","Animals","Drosophila","Female","Subcellular Fractions"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T15:33:51.526172Z","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":[]}