{"doi":"10.1038/ncomms9362","title":"Presynaptic spinophilin tunes neurexin signalling to control active zone architecture and function","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>\n                    Assembly and maturation of synapses at the\n                    <jats:italic>Drosophila</jats:italic>\n                    neuromuscular junction (NMJ) depend on trans-synaptic neurexin/neuroligin signalling, which is promoted by the scaffolding protein Syd-1 binding to neurexin. Here we report that the scaffold protein spinophilin binds to the C-terminal portion of neurexin and is needed to limit neurexin/neuroligin signalling by acting antagonistic to Syd-1. Loss of presynaptic spinophilin results in the formation of excess, but atypically small active zones. Neuroligin-1/neurexin-1/Syd-1 levels are increased at\n                    <jats:italic>spinophilin</jats:italic>\n                    mutant NMJs, and removal of single copies of the\n                    <jats:italic>neurexin-1, Syd-1</jats:italic>\n                    or\n                    <jats:italic>neuroligin-1</jats:italic>\n                    genes suppresses the spinophilin-active zone phenotype. Evoked transmission is strongly reduced at\n                    <jats:italic>spinophilin</jats:italic>\n                    terminals, owing to a severely reduced release probability at individual active zones. We conclude that presynaptic spinophilin fine-tunes neurexin/neuroligin signalling to control active zone number and functionality, thereby optimizing them for action potential-induced exocytosis.\n                  </jats:p>","journal":"Nature Communications","year":2015,"id":626260,"datarank":0.6515708132780527,"base_score":4.343805421853684,"endowment":4.343805421853684,"self_citation_contribution":0.6515708132780527,"citation_network_contribution":0.0,"self_endowment_contribution":0.6515708132780527,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":76,"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":1619922,"name":"Suneel Reddy-Alla","orcid":null,"position":1,"is_corresponding":false},{"id":1619923,"name":"Jan H Driller","orcid":null,"position":2,"is_corresponding":false},{"id":147918,"name":"Dietmar Schreiner","orcid":null,"position":3,"is_corresponding":false},{"id":1619924,"name":"Ulises Rey","orcid":null,"position":4,"is_corresponding":false},{"id":317267,"name":"Mathias A. Böhme","orcid":"0000-0002-0947-9172","position":5,"is_corresponding":false},{"id":1619925,"name":"Christina Hollmann","orcid":null,"position":6,"is_corresponding":false},{"id":1619926,"name":"Niraja Ramesh","orcid":null,"position":7,"is_corresponding":false},{"id":1030704,"name":"Harald Depner","orcid":"0000-0002-5285-0248","position":8,"is_corresponding":false},{"id":1030703,"name":"Janine Lützkendorf","orcid":"0000-0001-5051-6281","position":9,"is_corresponding":false},{"id":1619927,"name":"Tanja Matkovic","orcid":null,"position":10,"is_corresponding":false},{"id":1397732,"name":"Torsten Götz","orcid":"0000-0002-5894-1474","position":11,"is_corresponding":false},{"id":1619928,"name":"Dominique D. Bergeron","orcid":null,"position":12,"is_corresponding":false},{"id":1279714,"name":"Jan Schmoranzer","orcid":"0000-0002-4482-7080","position":13,"is_corresponding":false},{"id":1619929,"name":"Fabian Goettfert","orcid":null,"position":14,"is_corresponding":false},{"id":1619930,"name":"Mathew Holt","orcid":null,"position":15,"is_corresponding":false},{"id":1569139,"name":"Markus C. Wahl","orcid":null,"position":16,"is_corresponding":false},{"id":44839,"name":"Stefan W. Hell","orcid":"0000-0002-9638-5077","position":17,"is_corresponding":false},{"id":247156,"name":"Peter Scheiffele","orcid":"0000-0002-9516-9399","position":18,"is_corresponding":false},{"id":317270,"name":"Alexander M. Walter","orcid":"0000-0001-5646-4750","position":19,"is_corresponding":false},{"id":270925,"name":"Bernhard Loll","orcid":"0000-0001-7928-4488","position":20,"is_corresponding":false},{"id":212812,"name":"Stephan J. Sigrist","orcid":"0000-0002-1698-5815","position":21,"is_corresponding":false},{"id":1619921,"name":"Karzan Muhammad","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Presynaptic spinophilin tunes neurexin signalling to control active zone architecture and function","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>\n                    Assembly and maturation of synapses at the\n                    <jats:italic>Drosophila</jats:italic>\n                    neuromuscular junction (NMJ) depend on trans-synaptic neurexin/neuroligin signalling, which is promoted by the scaffolding protein Syd-1 binding to neurexin. Here we report that the scaffold protein spinophilin binds to the C-terminal portion of neurexin and is needed to limit neurexin/neuroligin signalling by acting antagonistic to Syd-1. Loss of presynaptic spinophilin results in the formation of excess, but atypically small active zones. Neuroligin-1/neurexin-1/Syd-1 levels are increased at\n                    <jats:italic>spinophilin</jats:italic>\n                    mutant NMJs, and removal of single copies of the\n                    <jats:italic>neurexin-1, Syd-1</jats:italic>\n                    or\n                    <jats:italic>neuroligin-1</jats:italic>\n                    genes suppresses the spinophilin-active zone phenotype. Evoked transmission is strongly reduced at\n                    <jats:italic>spinophilin</jats:italic>\n                    terminals, owing to a severely reduced release probability at individual active zones. We conclude that presynaptic spinophilin fine-tunes neurexin/neuroligin signalling to control active zone number and functionality, thereby optimizing them for action potential-induced exocytosis.\n                  </jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26471740","pmcid":"PMC4633989","openalex_id":null,"authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.nature.com/articles/ncomms9362.pdf","host_type":"publisher"},{"url":"https://www.nature.com/articles/ncomms9362","host_type":"publisher"},{"url":"https://lirias.kuleuven.be/handle/123456789/515523","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4633989","host_type":"repository"},{"url":"https://www.nature.com/articles/ncomms9362#supplementary-information","host_type":"repository"},{"url":"https://www.helmholtz-berlin.de/pubbin/oai_publication?VT=1ID=107164","host_type":"repository"},{"url":"https://resolver.sub.uni-goettingen.de/purl?gro-2/1346","host_type":"repository"},{"url":"http://hdl.handle.net/11858/00-001M-0000-0029-1EE8-2","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC4633989","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC4633989?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":[],"mesh_terms":["Synapses","Animals","Drosophila","Microfilament Proteins","GTPase-Activating Proteins","Cell Adhesion Molecules, Neuronal","Drosophila Proteins","Nerve Tissue Proteins","Female","Male","PDZ Domains","Neurabins"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-04T13:07:51.285411Z","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":[]}