{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:38:06Z","timestamp":1787567886862,"version":"build-2736575974"},"reference-count":70,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018232","name":"Orphan Disease Center, Perelman School of Medicine, University of Pennsylvania","doi-asserted-by":"publisher","award":["MDBR-21-103-CHM"],"award-info":[{"award-number":["MDBR-21-103-CHM"]}],"id":[{"id":"10.13039\/100018232","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001694","name":"International Retinal Research Foundation","doi-asserted-by":"publisher","award":["IRRF Grant"],"award-info":[{"award-number":["IRRF Grant"]}],"id":[{"id":"10.13039\/100001694","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["FISR2020IP_03551"],"award-info":[{"award-number":["FISR2020IP_03551"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["PNRR_PRIN_P2022NPLZC"],"award-info":[{"award-number":["PNRR_PRIN_P2022NPLZC"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["MIUR PRIN _2022WJFN5X"],"award-info":[{"award-number":["MIUR PRIN _2022WJFN5X"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013918","name":"Sanfilippo Children's Foundation","doi-asserted-by":"publisher","award":["SCF GRANT"],"award-info":[{"award-number":["SCF GRANT"]}],"id":[{"id":"10.13039\/100013918","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013927","name":"National MPS Society","doi-asserted-by":"publisher","award":["MPS GRANT"],"award-info":[{"award-number":["MPS GRANT"]}],"id":[{"id":"10.13039\/100013927","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Endosomes have emerged as major signaling hubs where different internalized ligand\u2013receptor complexes are integrated and the outcome of signaling pathways are organized to regulate the strength and specificity of signal transduction events. Ezrin, a major membrane\u2013actin linker that assembles and coordinates macromolecular signaling complexes at membranes, has emerged recently as an important regulator of lysosomal function. Here, we report that endosomal-localized EGFR\/Ezrin complex interacts with and triggers the inhibition of the Tuberous Sclerosis Complex (TSC complex) in response to EGF stimuli. This is regulated through activation of the AKT signaling pathway. Loss of Ezrin was not sufficient to repress TSC complex by EGF and culminated in translocation of TSC complex to lysosomes triggering suppression of mTORC1 signaling. Overexpression of constitutively active EZRIN\n                    <jats:sup>T567D<\/jats:sup>\n                    is sufficient to relocalize TSC complex to the endosomes and reactivate mTORC1. Our findings identify EZRIN as a critical regulator of autophagy via TSC complex in response to EGF stimuli and establish the central role of early endosomal signaling in the regulation of mTORC1. Consistently, Medaka fish deficient for Ezrin exhibit defective endo-lysosomal pathway, attributable to the compromised EGFR\/AKT signaling, ultimately leading to retinal degeneration. Our data identify a pivotal mechanism of endo-lysosomal signaling involving Ezrin and its associated EGFR\/TSC complex, which are essential for retinal function.\n                  <\/jats:p>","DOI":"10.7554\/elife.98523","type":"journal-article","created":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T08:25:47Z","timestamp":1723105547000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.98523","source":"Crossref","is-referenced-by-count":1,"title":["Ezrin defines TSC complex activation at endosomal compartments through EGFR\u2013AKT signaling"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3101-4697","authenticated-orcid":true,"given":"Giuliana","family":"Giamundo","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05290cv24","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, University of Naples Federico II","place":["Naples, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Daniela","family":"Intartaglia","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05290cv24","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, University of Naples Federico II","place":["Naples, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3214-9021","authenticated-orcid":true,"given":"Eugenio","family":"Del Prete","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04xfdsg27","id-type":"ROR","asserted-by":"publisher"}],"name":"Telethon Institute of Genetics and Medicine","place":["Pozzuoli, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Elena","family":"Polishchuk","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04xfdsg27","id-type":"ROR","asserted-by":"publisher"}],"name":"Telethon Institute of Genetics and Medicine","place":["Pozzuoli, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Fabrizio","family":"Andreone","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04xfdsg27","id-type":"ROR","asserted-by":"publisher"}],"name":"Telethon Institute of Genetics and Medicine","place":["Pozzuoli, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3698-9319","authenticated-orcid":true,"given":"Marzia","family":"Ognibene","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0424g0k78","id-type":"ROR","asserted-by":"publisher"}],"name":"U.O.C. Genetica Medica, IRCCS Istituto Giannina Gaslini","place":["Genova, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Sara","family":"Buonocore","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05290cv24","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, University of Naples Federico II","place":["Naples, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5579-183X","authenticated-orcid":true,"given":"Bruno","family":"Hay Mele","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05290cv24","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, University of Naples Federico II","place":["Naples, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Francesco Giuseppe","family":"Salierno","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04xfdsg27","id-type":"ROR","asserted-by":"publisher"}],"name":"Telethon Institute of Genetics and Medicine","place":["Pozzuoli, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Jlenia","family":"Monfregola","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04xfdsg27","id-type":"ROR","asserted-by":"publisher"}],"name":"Telethon Institute of Genetics and Medicine","place":["Pozzuoli, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Dario","family":"Antonini","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05290cv24","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, University of Naples Federico II","place":["Naples, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9942-9389","authenticated-orcid":true,"given":"Paolo","family":"Grumati","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04xfdsg27","id-type":"ROR","asserted-by":"publisher"}],"name":"Telethon Institute of Genetics and Medicine","place":["Pozzuoli, Italy"]},{"id":[{"id":"https:\/\/ror.org\/05290cv24","id-type":"ROR","asserted-by":"publisher"}],"name":"Clinical Medicine and Surgery, University of Naples Federico II","place":["Naples, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Alessandra","family":"Eva","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0424g0k78","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Molecular Biology, IRCCS Istituto Giannina Gaslini","place":["Genova, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Rossella","family":"De Cegli","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04xfdsg27","id-type":"ROR","asserted-by":"publisher"}],"name":"Telethon Institute of Genetics and Medicine","place":["Pozzuoli, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8968-9021","authenticated-orcid":true,"given":"Ivan","family":"Conte","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05290cv24","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, University of Naples Federico II","place":["Naples, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","type":"journal-article","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075113","type":"journal-article","article-title":"\u00df1 integrin binding phosphorylates ezrin at T567 to activate a lipid raft signalsome driving invadopodia activity and invasion","volume":"8","author":"Antelmi","year":"2013","journal-title":"PLOS ONE"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"2419","DOI":"10.1074\/jbc.M805311200","type":"journal-article","article-title":"Moesin regulates the trafficking of nascent clathrin-coated vesicles","volume":"284","author":"Barroso-Gonz\u00e1lez","year":"2009","journal-title":"The Journal of Biological Chemistry"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1111\/j.1365-2818.2006.01706.x","type":"journal-article","article-title":"A guided tour into subcellular colocalization analysis in light microscopy","volume":"224","author":"Bolte","year":"2006","journal-title":"Journal of Microscopy"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1016\/j.exer.2005.09.013","type":"journal-article","article-title":"Microvilli defects in retinas of ezrin knockout mice","volume":"82","author":"Bonilha","year":"2006","journal-title":"Experimental Eye Research"},{"key":"bib6","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-78201-9","type":"journal-article","article-title":"Photoreceptor alteration in intermediate age-related macular degeneration","volume":"10","author":"Borrelli","year":"2020","journal-title":"Scientific Reports"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/onc.2011.245","type":"journal-article","article-title":"Small molecule inhibitors of ezrin inhibit the invasive phenotype of osteosarcoma cells","volume":"31","author":"Bulut","year":"2012","journal-title":"Oncogene"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1091\/mbc.12.6.1897","type":"journal-article","article-title":"Regulation of epidermal growth factor receptor signaling by endocytosis and intracellular trafficking","volume":"12","author":"Burke","year":"2001","journal-title":"Molecular Biology of the Cell"},{"key":"bib9","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111601","type":"journal-article","article-title":"Targeting the MITF\/APAF-1 axis as salvage therapy for MAPK inhibitors in resistant melanoma","volume":"41","author":"Carotenuto","year":"2022","journal-title":"Cell Reports"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"72","DOI":"10.3390\/ijms14010072","type":"journal-article","article-title":"Spatial regulation of epidermal growth factor receptor signaling by endocytosis","volume":"14","author":"Ceresa","year":"2012","journal-title":"International Journal of Molecular Sciences"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"2661","DOI":"10.1091\/mbc.e05-09-0843","type":"journal-article","article-title":"The NHE3 juxtamembrane cytoplasmic domain directly binds ezrin: dual role in NHE3 trafficking and mobility in the brush border","volume":"17","author":"Cha","year":"2006","journal-title":"Molecular Biology of the Cell"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1091\/mbc.E10-09-0796","type":"journal-article","article-title":"The ERM proteins interact with the HOPS complex to regulate the maturation of endosomes","volume":"22","author":"Chirivino","year":"2011","journal-title":"Molecular Biology of the Cell"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"12813","DOI":"10.1073\/pnas.192084599","type":"journal-article","article-title":"Molecular analysis of microscopic ezrin dynamics by two-photon FRAP","volume":"99","author":"Coscoy","year":"2002","journal-title":"PNAS"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.tcb.2015.06.002","type":"journal-article","article-title":"Regulation of mTORC1 by PI3K signaling","volume":"25","author":"Dibble","year":"2015","journal-title":"Trends in Cell Biology"},{"key":"bib15","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202216877","type":"journal-article","article-title":"TFEB and TFE3 drive kidney cystogenesis and tumorigenesis","volume":"15","author":"Di Malta","year":"2023","journal-title":"EMBO Molecular Medicine"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","type":"journal-article","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1093\/nar\/30.1.207","type":"journal-article","article-title":"Gene Expression Omnibus: NCBI gene expression and hybridization array data repository","volume":"30","author":"Edgar","year":"2002","journal-title":"Nucleic Acids Research"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"7300","DOI":"10.1073\/pnas.96.13.7300","type":"journal-article","article-title":"Ezrin, a plasma membrane-microfilament linker, signals cell survival through the phosphatidylinositol 3-kinase\/Akt pathway","volume":"96","author":"Gautreau","year":"1999","journal-title":"PNAS"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"44180","DOI":"10.1074\/jbc.M207211200","type":"journal-article","article-title":"The TSC1 tumor suppressor hamartin interacts with neurofilament-L and possibly functions as a novel integrator of the neuronal cytoskeleton","volume":"277","author":"Haddad","year":"2002","journal-title":"The Journal of Biological Chemistry"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/nar\/gkn923","type":"journal-article","article-title":"Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists","volume":"37","author":"Huang","year":"2009","journal-title":"Nucleic Acids Research"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nprot.2008.211","type":"journal-article","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nature Protocols"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.7150\/thno.26281","type":"journal-article","article-title":"Abnormal mTORC1 signaling leads to retinal pigment epithelium degeneration","volume":"9","author":"Huang","year":"2019","journal-title":"Theranostics"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.mod.2004.03.012","type":"journal-article","article-title":"Stages of normal development in the medaka Oryzias latipes","volume":"121","author":"Iwamatsu","year":"2004","journal-title":"Mechanisms of Development"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1007\/978-3-319-75402-4_41","type":"journal-article","article-title":"Early endosome morphology in health and disease","volume":"1074","author":"Kaur","year":"2018","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"bib25","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23063246","type":"journal-article","article-title":"Pathophysiological roles of actin-binding scaffold protein, ezrin","volume":"23","author":"Kawaguchi","year":"2022","journal-title":"International Journal of Molecular Sciences"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1046\/j.1440-169x.2000.00530.x","type":"journal-article","article-title":"Activity of the medaka translation elongation factor 1alpha-A promoter examined using the GFP gene as A reporter","volume":"42","author":"Kinoshita","year":"2000","journal-title":"Development, Growth & Differentiation"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1007\/s10585-006-9033-y","type":"journal-article","article-title":"Ezrin mediates growth and survival in Ewing\u2019s sarcoma through the AKT\/mTOR, but not the MAPK, signaling pathway","volume":"23","author":"Krishnan","year":"2006","journal-title":"Clinical & Experimental Metastasis"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1038\/s41416-019-0383-z","type":"journal-article","article-title":"Ezrin promotes breast cancer progression by modulating AKT signals","volume":"120","author":"Li","year":"2019","journal-title":"British Journal of Cancer"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1016\/j.cell.2007.05.041","type":"journal-article","article-title":"Structural basis for the autoinhibition of focal adhesion kinase","volume":"129","author":"Lietha","year":"2007","journal-title":"Cell"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"7532","DOI":"10.1523\/JNEUROSCI.1004-06.2006","type":"journal-article","article-title":"Epidermal growth factor receptor activation: an upstream signal for transition of quiescent astrocytes into reactive astrocytes after neural injury","volume":"26","author":"Liu","year":"2006","journal-title":"The Journal of Neuroscience"},{"key":"bib31","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2020.114095","type":"journal-article","article-title":"Transcriptional activation of cyclin D1 via HER2\/HER3 contributes to EGFR-TKI resistance in lung cancer","volume":"178","author":"Liu","year":"2020","journal-title":"Biochemical Pharmacology"},{"key":"bib32","doi-asserted-by":"publisher","DOI":"10.3791\/62528","type":"journal-article","article-title":"Three differential expression analysis methods for rna sequencing: limma, EdgeR, DESeq2","volume":"175","author":"Liu","year":"2021","journal-title":"Journal of Visualized Experiments"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1038\/s41587-022-01539-0","type":"journal-article","article-title":"A proteome-wide atlas of drug mechanism of action","volume":"41","author":"Mitchell","year":"2023","journal-title":"Nature Biotechnology"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"2072","DOI":"10.1080\/15548627.2017.1380124","type":"journal-article","article-title":"RUBCN\/rubicon and EGFR regulate lysosomal degradative processes in the retinal pigment epithelium (RPE) of the eye","volume":"13","author":"Muniz-Feliciano","year":"2017","journal-title":"Autophagy"},{"key":"bib35","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2019102468","type":"journal-article","article-title":"Light-responsive microRNA miR-211 targets Ezrin to modulate lysosomal biogenesis and retinal cell clearance","volume":"39","author":"Naso","year":"2020","journal-title":"The EMBO Journal"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.3892\/ijo.2015.2871","type":"journal-article","article-title":"EGF\u2011stimulated AKT activation is mediated by EGFR recycling via an early endocytic pathway in a gefitinib\u2011resistant human lung cancer cell line","volume":"46","author":"Nishimura","year":"2015","journal-title":"International Journal of Oncology"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"29973","DOI":"10.1074\/jbc.M111.270785","type":"journal-article","article-title":"The tumor suppressor hamartin enhances Dbl protein transforming activity through interaction with ezrin","volume":"286","author":"Ognibene","year":"2011","journal-title":"The Journal of Biological Chemistry"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/j.cell.2006.09.026","type":"journal-article","article-title":"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks","volume":"127","author":"Olsen","year":"2006","journal-title":"Cell"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1074\/mcp.m200025-mcp200","type":"journal-article","article-title":"Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics","volume":"1","author":"Ong","year":"2002","journal-title":"Molecular & Cellular Proteomics"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1002\/pro.3978","type":"journal-article","article-title":"The BioGRID database: A comprehensive biomedical resource of curated protein, genetic, and chemical interactions","volume":"30","author":"Oughtred","year":"2021","journal-title":"Protein Science"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/j.tcb.2012.06.004","type":"journal-article","article-title":"Endosomal crosstalk: meeting points for signaling pathways","volume":"22","author":"P\u00e1lfy","year":"2012","journal-title":"Trends in Cell Biology"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"2017","DOI":"10.4049\/jimmunol.1201292","type":"journal-article","article-title":"Spatial coupling of JNK activation to the B cell antigen receptor by tyrosine-phosphorylated Ezrin","volume":"190","author":"Parameswaran","year":"2013","journal-title":"The Journal of Immunology"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/nmeth.2895","type":"journal-article","article-title":"The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein interactions in human cells","volume":"11","author":"Petschnigg","year":"2014","journal-title":"Nature Methods"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1002\/pro.3943","type":"journal-article","article-title":"UCSF ChimeraX: structure visualization for researchers, educators, and developers","volume":"30","author":"Pettersen","year":"2021","journal-title":"Protein Science"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"5773","DOI":"10.1093\/nar\/gkw486","type":"journal-article","article-title":"An atlas of gene expression and gene co-regulation in the human retina","volume":"44","author":"Pinelli","year":"2016","journal-title":"Nucleic Acids Research"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"2341","DOI":"10.1002\/1873-3468.13575","type":"journal-article","article-title":"From and to the Golgi - defining the Wilson disease protein road map","volume":"593","author":"Polishchuk","year":"2019","journal-title":"FEBS Letters"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"4015","DOI":"10.1091\/mbc.e03-01-0040","type":"journal-article","article-title":"The role of mVps18p in clustering, fusion, and intracellular localization of late endocytic organelles","volume":"14","author":"Poupon","year":"2003","journal-title":"Molecular Biology of the Cell"},{"key":"bib48","type":"software","article-title":"R: A language and environment for statistical computing","author":"R Development Core Team","year":"2024","unstructured":"R Development Core Team. 2024. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing. https:\/\/www.R-project.org\/."},{"key":"bib49","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1590\/1678-4685-GMB-2015-0321","type":"journal-article","article-title":"TSC1 and TSC2 gene mutations and their implications for treatment in tuberous sclerosis complex: a review","volume":"40","author":"Rosset","year":"2017","journal-title":"Genetics and Molecular Biology"},{"key":"bib50","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202154041","type":"journal-article","article-title":"Physical and functional interactome atlas of human receptor tyrosine kinases","volume":"23","author":"Salokas","year":"2022","journal-title":"EMBO Reports"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.neo.2016.01.002","type":"journal-article","article-title":"Ezrin enhances EGFR signaling and modulates erlotinib sensitivity in non-small cell lung cancer cells","volume":"18","author":"Saygide\u011fer-Kont","year":"2016","journal-title":"Neoplasia"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","type":"journal-article","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nature Methods"},{"key":"bib53","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-02386-6","type":"journal-article","article-title":"\u03b2A3\/A1-crystallin regulates apical polarity and EGFR endocytosis in retinal pigmented epithelial cells","volume":"4","author":"Shang","year":"2021","journal-title":"Communications Biology"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1016\/j.str.2020.06.007","type":"journal-article","article-title":"MAP kinase-mediated activation of RSK1 and MK2 substrate kinases","volume":"28","author":"Sok","year":"2020","journal-title":"Structure"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1038\/nrm2748","type":"journal-article","article-title":"Endocytosis and signalling: intertwining molecular networks","volume":"10","author":"Sorkin","year":"2009","journal-title":"Nature Reviews. Molecular Cell Biology"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"4354","DOI":"10.1074\/jbc.M511989200","type":"journal-article","article-title":"Ezrin directly interacts with the alpha1b-adrenergic receptor and plays a role in receptor recycling","volume":"281","author":"Stanasila","year":"2006","journal-title":"The Journal of Biological Chemistry"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"3623","DOI":"10.1242\/jcs.02495","type":"journal-article","article-title":"Actin remodeling requires ERM function to facilitate AQP2 apical targeting","volume":"118","author":"Tamma","year":"2005","journal-title":"Journal of Cell Science"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"2288","DOI":"10.1074\/jbc.M117.811299","type":"journal-article","article-title":"Ligand-activated epidermal growth factor receptor (EGFR) signaling governs endocytic trafficking of unliganded receptor monomers by non-canonical phosphorylation","volume":"293","author":"Tanaka","year":"2018","journal-title":"Journal of Biological Chemistry"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.exer.2014.05.003","type":"journal-article","article-title":"A detailed three-step protocol for live imaging of intracellular traffic in polarized primary porcine RPE monolayers","volume":"124","author":"Toops","year":"2014","journal-title":"Experimental Eye Research"},{"key":"bib60","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.37262","type":"journal-article","article-title":"Ezrin enrichment on curved membranes requires a specific conformation or interaction with a curvature-sensitive partner","volume":"7","author":"Tsai","year":"2018","journal-title":"eLife"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1111\/tra.12271","type":"journal-article","article-title":"Ultrastructural morphometry points to a new role for lamtor2 in regulating the endo\/lysosomal system","volume":"16","author":"Vogel","year":"2015","journal-title":"Traffic"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"2406","DOI":"10.1158\/0008-5472.CAN-04-3135","type":"journal-article","article-title":"Rapamycin inhibits ezrin-mediated metastatic behavior in a murine model of osteosarcoma","volume":"65","author":"Wan","year":"2005","journal-title":"Cancer Research"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"7279","DOI":"10.1128\/MCB.22.20.7279-7290.2002","type":"journal-article","article-title":"Endosomal signaling of epidermal growth factor receptor stimulates signal transduction pathways leading to cell survival","volume":"22","author":"Wang","year":"2002","journal-title":"Molecular and Cellular Biology"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"W214","DOI":"10.1093\/nar\/gkq537","type":"journal-article","article-title":"The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function","volume":"38","author":"Warde-Farley","year":"2010","journal-title":"Nucleic Acids Research"},{"key":"bib65","doi-asserted-by":"publisher","DOI":"10.3390\/cancers9050052","type":"journal-article","article-title":"Epidermal growth factor receptor cell proliferation signaling pathways","volume":"9","author":"Wee","year":"2017","journal-title":"Cancers"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"9485","DOI":"10.1073\/pnas.0308400101","type":"journal-article","article-title":"Ezrin regulates NHE3 translocation and activation after Na+-glucose cotransport","volume":"101","author":"Zhao","year":"2004","journal-title":"PNAS"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"35651","DOI":"10.1074\/jbc.M303416200","type":"journal-article","article-title":"Characterization of protein kinase A-mediated phosphorylation of ezrin in gastric parietal cell activation","volume":"278","author":"Zhou","year":"2003","journal-title":"The Journal of Biological Chemistry"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"4381","DOI":"10.1242\/jcs.02559","type":"journal-article","article-title":"Phosphorylation of ezrin on threonine 567 produces a change in secretory phenotype and repolarizes the gastric parietal cell","volume":"118","author":"Zhou","year":"2005","journal-title":"Journal of Cell Science"},{"key":"dataset1","type":"dataset","article-title":"Transcriptome profile of EZR_KO cells","volume-title":"NCBI Gene Expression Omnibus","author":"De Cegli","year":"2025","unstructured":"De Cegli R. 2025. Transcriptome profile of EZR_KO cells. NCBI Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE195983. GSE195983."},{"key":"dataset2","type":"dataset","article-title":"Ezrin defines TSC1 activation at endosomal compartment through EGFR-AKT signaling","volume-title":"PRIDE","author":"De Cegli","year":"2025","unstructured":"De Cegli R. 2025. Ezrin defines TSC1 activation at endosomal compartment through EGFR-AKT signaling. PRIDE. http:\/\/www.ebi.ac.uk\/pride\/archive\/projects\/PXD045157. PXD045157."}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/98523\/elife-98523-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/98523\/elife-98523-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/98523","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:53:40Z","timestamp":1787565220000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/98523"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,12]]},"references-count":70,"alternative-id":["10.7554\/eLife.98523"],"URL":"https:\/\/doi.org\/10.7554\/elife.98523","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.05.03.592332","asserted-by":"subject"}],"is-same-as":[{"id-type":"doi","id":"10.7554\/eLife.98523.3","asserted-by":"subject"}],"is-version-of":[{"id-type":"doi","id":"10.7554\/eLife.98523.1","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.98523.2","asserted-by":"subject"}],"is-supplemented-by":[{"id-type":"accession","id":"GSE195983","asserted-by":"subject"},{"id-type":"accession","id":"PXD045157","asserted-by":"subject"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,12]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"RP98523"}}