{"doi":"10.1073/pnas.0307862100","title":"Functional dissection of the interactions of stonin 2 with the adaptor complex AP-2 and synaptotagmin","abstract":"<jats:p>Synaptic vesicle recycling is in part mediated by clathrin-mediated endocytosis. This process involves the coordinated assembly of clathrin and adaptor proteins and the concomitant selection of cargo proteins. Here, we demonstrate that the endocytotic protein stonin 2 localizes to axonal vesicle clusters through its μ-homology domain. Interaction of this domain with synaptotagmin I is sufficient to recruit stonin 2 to the plasmalemma. The N-terminal domain of stonin 2 harbors multiple AP-2-interaction motifs that bind to the clathrin adaptor complex AP-2. These motifs with the consensus sequence WVxF are capable of binding to the α-adaptin ear domain and to μ2. Mutation of the tyrosine motif-binding pocket of μ2 abolishes recognition of the WVxF peptide, suggesting that association with stonin 2 renders AP-2 incompetent to sort tyrosine motif-containing cargo proteins. We hypothesize that stonin 2 may function as an AP-2-dependent sorting adaptor for synaptic vesicle recycling.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2004,"id":655878,"datarank":0.6830815337400812,"base_score":4.553876891600541,"endowment":4.553876891600541,"self_citation_contribution":0.6830815337400812,"citation_network_contribution":0.0,"self_endowment_contribution":0.6830815337400812,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":94,"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":1712100,"name":"M. Kasim Diril","orcid":null,"position":1,"is_corresponding":false},{"id":1712101,"name":"Nadja Jung","orcid":null,"position":2,"is_corresponding":false},{"id":71008,"name":"Volker Haucke","orcid":"0000-0003-3119-6993","position":3,"is_corresponding":false},{"id":1712098,"name":"Kristin Walther","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Functional dissection of the interactions of stonin 2 with the adaptor complex AP-2 and synaptotagmin","abstract":"<jats:p>Synaptic vesicle recycling is in part mediated by clathrin-mediated endocytosis. This process involves the coordinated assembly of clathrin and adaptor proteins and the concomitant selection of cargo proteins. Here, we demonstrate that the endocytotic protein stonin 2 localizes to axonal vesicle clusters through its μ-homology domain. Interaction of this domain with synaptotagmin I is sufficient to recruit stonin 2 to the plasmalemma. The N-terminal domain of stonin 2 harbors multiple AP-2-interaction motifs that bind to the clathrin adaptor complex AP-2. These motifs with the consensus sequence WVxF are capable of binding to the α-adaptin ear domain and to μ2. Mutation of the tyrosine motif-binding pocket of μ2 abolishes recognition of the WVxF peptide, suggesting that association with stonin 2 renders AP-2 incompetent to sort tyrosine motif-containing cargo proteins. We hypothesize that stonin 2 may function as an AP-2-dependent sorting adaptor for synaptic vesicle recycling.</jats:p>","is_dataset_classified":null,"base_score":4.553876891600541,"endowment":4.553876891600541,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"14726597","pmcid":"PMC327125","openalex_id":"https://openalex.org/W2093994138","authors":[],"funders":[],"total_grants":0,"fwci":3.8817,"citation_percentile":0.94114381,"influential_citations":0,"citation_trend":[{"year":2012,"count":7},{"year":2013,"count":1},{"year":2014,"count":2},{"year":2015,"count":5},{"year":2017,"count":7},{"year":2018,"count":1},{"year":2019,"count":1},{"year":2020,"count":2},{"year":2021,"count":4},{"year":2023,"count":3},{"year":2024,"count":1},{"year":2025,"count":2}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/327125","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/327125","host_type":"repository"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.0307862100","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.0307862100","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/14726597","host_type":"repository"}],"fields_of_study":["Cellular transport and secretion","Lipid Membrane Structure and Behavior","Erythrocyte Function and Pathophysiology","Adaptor Protein Complex 2","Adaptor Protein Complex alpha Subunits","Adaptor Proteins, Vesicular Transport","Amino Acid Sequence","Animals","Brain","Calcium-Binding Proteins","Carrier Proteins","Cell Line","Endocytosis","Humans","Membrane Glycoproteins","Membrane Proteins","Molecular Sequence Data","Mutagenesis, Site-Directed","Nerve Tissue Proteins","Protein Binding","Synaptotagmin I","Synaptotagmins","Transferrin","Vesicular Transport Proteins"],"mesh_terms":["Amino Acid Sequence","Animals","Brain","Calcium-Binding Proteins","Carrier Proteins","Cell Line","Endocytosis","Humans","Membrane Glycoproteins","Membrane Proteins","Molecular Sequence Data","Nerve Tissue Proteins","Protein Binding","Transferrin","Mutagenesis, Site-Directed","Vesicular Transport Proteins","Adaptor Proteins, Vesicular Transport","Adaptor Protein Complex 2","Adaptor Protein Complex alpha Subunits","Synaptotagmins","Synaptotagmin I"],"keywords":["Signal transducing adaptor protein","Clathrin","Synaptotagmin 1","Clathrin adaptor proteins","Amphiphysin","Cell biology","Synaptotagmin I","Biology","Phosphotyrosine-binding domain","Endocytosis","Vesicle","Synaptic vesicle","Chemistry","Biochemistry","SH2 domain","Proto-oncogene tyrosine-protein kinase Src","Signal transduction","Dynamin","Receptor"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life below water"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-11T19:12:13.855099Z","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":[]}