{"doi":"10.1091/mbc.e07-10-0997","title":"Eps15 Mediates Vesicle Trafficking from the<i>trans</i>-Golgi Network via an Interaction with the Clathrin Adaptor AP-1","abstract":"<jats:p>Eps15 (EGFR pathway substrate clone 15) is well known for its role in clathrin-coated vesicle formation at the plasma membrane through interactions with other clathrin adaptor proteins such as AP-2. Interestingly, we observed that in addition to its plasma membrane localization, Eps15 is also present at the trans-Golgi network (TGN). Therefore, we predicted that Eps15 might associate with clathrin adaptor proteins at the TGN and thereby mediate the formation of Golgi-derived vesicles. Indeed, we have found that Eps15 and the TGN clathrin adaptor AP-1 coimmunoprecipitate from rat liver Golgi fractions. Furthermore, we have identified a 14-amino acid motif near the AP-2–binding domain of Eps15 that is required for binding to AP-1, but not AP-2. Disruption of the Eps15–AP-1 interaction via siRNA knockdown of AP-1 or expression of mutant Eps15 protein, which lacks a 14-amino acid motif representing the AP-1 binding site of Eps15, significantly reduced the exit of secretory proteins from the TGN. Together, these findings indicate that Eps15 plays an important role in clathrin-coated vesicle formation not only at the plasma membrane but also at the TGN during the secretory process.</jats:p>","journal":"Molecular Biology of the Cell","year":2008,"id":629996,"datarank":0.5641800173540344,"base_score":3.7612001156935624,"endowment":3.7612001156935624,"self_citation_contribution":0.5641800173540344,"citation_network_contribution":0.0,"self_endowment_contribution":0.5641800173540344,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":42,"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":150333,"name":"Hong Cao","orcid":null,"position":1,"is_corresponding":false},{"id":524934,"name":"Jing Chen","orcid":"0000-0001-9658-0713","position":2,"is_corresponding":false},{"id":463876,"name":"Mark A. McNiven","orcid":"0000-0002-9830-1885","position":3,"is_corresponding":false},{"id":18802,"name":"Susan Chi","orcid":"0000-0001-7753-878X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Eps15 Mediates Vesicle Trafficking from the<i>trans</i>-Golgi Network via an Interaction with the Clathrin Adaptor AP-1","abstract":"<jats:p>Eps15 (EGFR pathway substrate clone 15) is well known for its role in clathrin-coated vesicle formation at the plasma membrane through interactions with other clathrin adaptor proteins such as AP-2. Interestingly, we observed that in addition to its plasma membrane localization, Eps15 is also present at the trans-Golgi network (TGN). Therefore, we predicted that Eps15 might associate with clathrin adaptor proteins at the TGN and thereby mediate the formation of Golgi-derived vesicles. Indeed, we have found that Eps15 and the TGN clathrin adaptor AP-1 coimmunoprecipitate from rat liver Golgi fractions. Furthermore, we have identified a 14-amino acid motif near the AP-2–binding domain of Eps15 that is required for binding to AP-1, but not AP-2. Disruption of the Eps15–AP-1 interaction via siRNA knockdown of AP-1 or expression of mutant Eps15 protein, which lacks a 14-amino acid motif representing the AP-1 binding site of Eps15, significantly reduced the exit of secretory proteins from the TGN. Together, these findings indicate that Eps15 plays an important role in clathrin-coated vesicle formation not only at the plasma membrane but also at the TGN during the secretory process.</jats:p>","is_dataset_classified":null,"base_score":3.7612001156935624,"endowment":3.7612001156935624,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"18524853","pmcid":"PMC2488291","openalex_id":"https://openalex.org/W2171090621","authors":[],"funders":[{"funder_name":"NIDDK NIH HHS","grant_id":"R37 DK044650","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R56 DK044650","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK044650","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK 44650","title":null}],"total_grants":4,"fwci":1.7749,"citation_percentile":0.83460246,"influential_citations":0,"citation_trend":[{"year":2012,"count":7},{"year":2013,"count":2},{"year":2014,"count":3},{"year":2015,"count":1},{"year":2016,"count":3},{"year":2017,"count":3},{"year":2019,"count":1},{"year":2020,"count":1},{"year":2021,"count":2},{"year":2022,"count":1},{"year":2023,"count":1},{"year":2024,"count":2},{"year":2026,"count":1}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2488291","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2488291","host_type":"repository"},{"url":"https://doi.org/10.1091/mbc.e07-10-0997","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/18524853","host_type":"repository"},{"url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.327.3441","host_type":""}],"fields_of_study":["Cellular transport and secretion","Lipid Membrane Structure and Behavior","RNA Interference and Gene Delivery","Adaptor Proteins, Signal Transducing","Amino Acid Motifs","Animals","Calcium-Binding Proteins","Cell Membrane","Clathrin","Cricetinae","Cricetulus","Endocytosis","Golgi Apparatus","HeLa Cells","Humans","Intracellular Signaling Peptides and Proteins","Liver","Models, Biological","Phosphoproteins","Rats","Transcription Factor AP-1","trans-Golgi Network"],"mesh_terms":["Animals","Calcium-Binding Proteins","Cell Membrane","Clathrin","Cricetulus","Endocytosis","Golgi Apparatus","Cricetinae","HeLa Cells","Humans","Liver","Models, Biological","Phosphoproteins","Transcription Factor AP-1","Amino Acid Motifs","trans-Golgi Network","Intracellular Signaling Peptides and Proteins","Adaptor Proteins, Signal Transducing","Rats","Hela Cells"],"keywords":["Clathrin","Signal transducing adaptor protein","Golgi apparatus","Biology","Cell biology","Vesicle","Clathrin adaptor proteins","Plasma protein binding","Phosphotyrosine-binding domain","Biochemistry","Membrane","Signal transduction","Endoplasmic reticulum"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"refseq"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T20:14:10.828795Z","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":[]}