{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:00:56Z","timestamp":1791223256763,"version":"4.1.0"},"reference-count":55,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,2,1]]},"abstract":"<jats:p>During neurotransmitter release, SVs (synaptic vesicles) fuse at the active zone and are recovered predominantly via clathrin-mediated endocytosis at the presynaptic compartment surrounding the site of release, referred to as the periactive zone. Exo- and endo-cytosis in synapses are tightly temporarily and spatially coupled to sustain synaptic transmission. The molecular mechanisms linking these two cellular events, which take place in separate compartments of the nerve terminal, remain largely enigmatic. Several lines of evidence indicate that multiple factors may be involved in exocytic\u2013endocytic coupling including SV integral membrane proteins, SV membrane lipids and the membrane-associated actin cytoskeleton. A number of recent studies also indicate that multimodular adaptor proteins shuttling between the active and periactive zones aid the dynamic assembly of macromolecular protein complexes that execute the exo- and endo-cytic limbs of the SV cycle. Here, we discuss recent evidence implicating the multidomain scaffolding and adaptor protein ITSN1 (intersectin 1) as a central regulator of SV cycling.<\/jats:p>","DOI":"10.1042\/bst0380181","type":"journal-article","created":{"date-parts":[[2010,1,20]],"date-time":"2010-01-20T16:17:54Z","timestamp":1264004274000},"page":"181-186","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Intersectin 1: a versatile actor in the synaptic vesicle cycle"],"prefix":"10.1042","volume":"38","author":[{"given":"Arndt","family":"Pechstein","sequence":"first","affiliation":[{"name":"Department of Membrane Biochemistry, Institute of Chemistry and Biochemistry, Freie Universit\u00e4t and Charit\u00e9-Universit\u00e4tsmedizin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg","family":"Shupliakov","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, DBRM, Karolinska Institutet, 17177 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Haucke","sequence":"additional","affiliation":[{"name":"Department of Membrane Biochemistry, Institute of Chemistry and Biochemistry, Freie Universit\u00e4t and Charit\u00e9-Universit\u00e4tsmedizin, Berlin, Germany"},{"name":"Leibniz Institute of Molecular Pharmacology, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2010,1,19]]},"reference":[{"key":"2021111720203797900_B1","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1083\/jcb.57.2.315","article-title":"Evidence for recycling of synaptic vesicle membrane during transmitter release at the frog neuromuscular junction","volume":"57","author":"Heuser","year":"1973","journal-title":"J. Cell Biol."},{"key":"2021111720203797900_B2","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1146\/annurev.neuro.26.041002.131445","article-title":"Cell biology of the presynaptic terminal","volume":"26","author":"Murthy","year":"2003","journal-title":"Annu. Rev. Neurosci."},{"key":"2021111720203797900_B3","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1146\/annurev.neuro.26.041002.131412","article-title":"The synaptic vesicle cycle","volume":"27","author":"S\u00fcdhof","year":"2004","journal-title":"Annu. Rev. Neurosci."},{"key":"2021111720203797900_B4","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1126\/science.1553547","article-title":"Optical analysis of synaptic vesicle recycling at the frog neuromuscular junction","volume":"255","author":"Betz","year":"1992","journal-title":"Science"},{"key":"2021111720203797900_B5","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1146\/annurev.cellbio.042308.113302","article-title":"Molecular circuitry of endocytosis at nerve terminals","volume":"25","author":"Dittman","year":"2009","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"2021111720203797900_B6","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.neuroscience.2008.03.035","article-title":"The synaptic vesicle cluster: a source of endocytic proteins during neurotransmitter release","volume":"158","author":"Shupliakov","year":"2009","journal-title":"Neuroscience"},{"key":"2021111720203797900_B7","first-page":"re19","article-title":"Cycling of synaptic vesicles: how far? How fast! Sci","volume":"2004","author":"Galli","year":"2004","journal-title":"STKE"},{"key":"2021111720203797900_B8","doi-asserted-by":"crossref","first-page":"3494","DOI":"10.1038\/sj.emboj.7601247","article-title":"Intersectin-1L nucleotide exchange factor regulates secretory granule exocytosis by activating Cdc42","volume":"25","author":"Malacombe","year":"2006","journal-title":"EMBO J."},{"key":"2021111720203797900_B9","doi-asserted-by":"crossref","first-page":"18446","DOI":"10.1074\/jbc.274.26.18446","article-title":"EHSH1\/intersectin, a protein that contains EH and SH3 domains and binds to dynamin and SNAP-25: a protein connection between exocytosis and endocytosis? J","volume":"274","author":"Okamoto","year":"1999","journal-title":"Biol. Chem."},{"key":"2021111720203797900_B10","doi-asserted-by":"crossref","first-page":"6300","DOI":"10.1038\/sj.onc.1204773","article-title":"Mitogenesis and endocytosis: what's at the intersection?","volume":"20","author":"O'Bryan","year":"2001","journal-title":"Oncogene"},{"key":"2021111720203797900_B11","doi-asserted-by":"crossref","first-page":"5091","DOI":"10.1091\/mbc.e07-05-0460","article-title":"Caenorhabditis elegans intersectin: a synaptic protein regulating neurotransmission","volume":"18","author":"Rose","year":"2007","journal-title":"Mol. Biol. Cell"},{"key":"2021111720203797900_B12","doi-asserted-by":"crossref","first-page":"19108","DOI":"10.1074\/jbc.273.30.19108","article-title":"Dap160, a neural-specific Eps15 homology and multiple SH3 domain-containing protein that interacts with Drosophila dynamin","volume":"273","author":"Roos","year":"1998","journal-title":"J. Biol. Chem."},{"key":"2021111720203797900_B13","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1093\/emboj\/18.5.1159","article-title":"The EH and SH3 domain Ese proteins regulate endocytosis by linking to dynamin and Eps15","volume":"18","author":"Sengar","year":"1999","journal-title":"EMBO J."},{"key":"2021111720203797900_B14","doi-asserted-by":"crossref","first-page":"31401","DOI":"10.1074\/jbc.273.47.31401","article-title":"Intersectin, a novel adaptor protein with two Eps15 homology and five Src homology 3 domains","volume":"273","author":"Yamabhai","year":"1998","journal-title":"J. Biol. Chem."},{"key":"2021111720203797900_B15","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.neuron.2004.06.029","article-title":"Dap160\/intersectin acts as a stabilizing scaffold required for synaptic development and vesicle endocytosis","volume":"43","author":"Koh","year":"2004","journal-title":"Neuron"},{"key":"2021111720203797900_B16","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.neuron.2004.07.001","article-title":"Dap160\/intersectin scaffolds the periactive zone to achieve high-fidelity endocytosis and normal synaptic growth","volume":"43","author":"Marie","year":"2004","journal-title":"Neuron"},{"key":"2021111720203797900_B17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0167-4781(01)00276-7","article-title":"The human intersectin genes and their spliced variants are differentially expressed","volume":"1521","author":"Pucharcos","year":"2001","journal-title":"Biochim. Biophys. Acta"},{"key":"2021111720203797900_B18","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ygeno.2004.02.005","article-title":"Alternative splicing of mammalian intersectin 1: domain associations and tissue specificities","volume":"84","author":"Tsyba","year":"2004","journal-title":"Genomics"},{"key":"2021111720203797900_B19","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1006\/geno.1998.5521","article-title":"Two isoforms of a human intersectin (ITSN) protein are produced by brain-specific alternative splicing in a stop codon","volume":"53","author":"Guipponi","year":"1998","journal-title":"Genomics"},{"key":"2021111720203797900_B20","doi-asserted-by":"crossref","first-page":"15671","DOI":"10.1074\/jbc.274.22.15671","article-title":"Splice variants of intersectin are components of the endocytic machinery in neurons and nonneuronal cells","volume":"274","author":"Hussain","year":"1999","journal-title":"J. Biol. Chem."},{"key":"2021111720203797900_B21","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/sj.ejhg.5200356","article-title":"Alu-splice cloning of human intersectin (ITSN), a putative multivalent binding protein expressed in proliferating and differentiating neurons and overexpressed in Down syndrome","volume":"7","author":"Pucharcos","year":"1999","journal-title":"Eur. J. Hum. Genet."},{"key":"2021111720203797900_B22","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1523\/JNEUROSCI.4683-06.2007","article-title":"Intersectin is a negative regulator of dynamin recruitment to the synaptic endocytic zone in the central synapse","volume":"27","author":"Evergren","year":"2007","journal-title":"J. Neurosci."},{"key":"2021111720203797900_B23","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1124\/mol.106.028274","article-title":"Intersectin regulates epidermal growth factor receptor endocytosis, ubiquitylation and signaling","volume":"70","author":"Martin","year":"2006","journal-title":"Mol. Pharmacol."},{"key":"2021111720203797900_B24","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1038\/ncb1001-927","article-title":"Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP","volume":"3","author":"Hussain","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"2021111720203797900_B25","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.brainresrev.2005.06.002","article-title":"Recycling and EH domain proteins at the synapse","volume":"49","author":"Montesinos","year":"2005","journal-title":"Brain Res. Rev."},{"key":"2021111720203797900_B26","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1006\/excr.1999.4694","article-title":"The EH network","volume":"253","author":"Santolini","year":"1999","journal-title":"Exp. Cell Res."},{"key":"2021111720203797900_B27","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/sj.emboj.7601980","article-title":"Structure of the Eps15\u2013stonin2 complex provides a molecular explanation for EH-domain ligand specificity","volume":"27","author":"Rumpf","year":"2008","journal-title":"EMBO J."},{"key":"2021111720203797900_B28","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1042\/BJ20041797","article-title":"Molecular and genetic characterization of the interactions between the Drosophila stoned-B protein and DAP-160 (intersectin)","volume":"388","author":"Kelly","year":"2005","journal-title":"Biochem. J."},{"key":"2021111720203797900_B29","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1083\/jcb.153.5.1111","article-title":"Stonin 2: an adaptor-like protein that interacts with components of the endocytic machinery","volume":"153","author":"Martina","year":"2001","journal-title":"J. Cell Biol."},{"key":"2021111720203797900_B30","doi-asserted-by":"crossref","first-page":"12752","DOI":"10.1074\/jbc.275.17.12752","article-title":"SCAMP1 function in endocytosis","volume":"275","author":"Fernandez-Chacon","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2021111720203797900_B31","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1083\/jcb.200701030","article-title":"Eps15 and Dap160 control synaptic vesicle membrane retrieval and synapse development","volume":"178","author":"Koh","year":"2007","journal-title":"J. Cell Biol."},{"key":"2021111720203797900_B32","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1111\/j.1600-0854.2008.00712.x","article-title":"ITSN-1 controls vesicle recycling at the neuromuscular junction and functions in parallel with DAB-1","volume":"9","author":"Wang","year":"2008","journal-title":"Traffic"},{"key":"2021111720203797900_B33","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1093\/emboj\/19.6.1263","article-title":"The endocytic protein intersectin is a major binding partner for the Ras exchange factor mSos1 in rat brain","volume":"19","author":"Tong","year":"2000","journal-title":"EMBO J."},{"key":"2021111720203797900_B34","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1016\/S0960-9822(00)80087-1","article-title":"The endocytic machinery in nerve terminals surrounds sites of exocytosis","volume":"9","author":"Roos","year":"1999","journal-title":"Curr. Biol."},{"key":"2021111720203797900_B35","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0014-5793(00)01793-2","article-title":"Intersectin 2, a new multimodular protein involved in clathrin-mediated endocytosis","volume":"478","author":"Pucharcos","year":"2000","journal-title":"FEBS Lett."},{"key":"2021111720203797900_B36","doi-asserted-by":"crossref","first-page":"12410","DOI":"10.1074\/jbc.M809746200","article-title":"Intersectin regulates dendritic spine development and somatodendritic endocytosis but not synaptic vesicle recycling in hippocampal neurons","volume":"284","author":"Thomas","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2021111720203797900_B37","doi-asserted-by":"crossref","first-page":"6445","DOI":"10.1073\/pnas.0710267105","article-title":"Role of epsin 1 in synaptic vesicle endocytosis","volume":"105","author":"Jakobsson","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021111720203797900_B38","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1111\/j.1398-9219.2004.00198.x","article-title":"Amphiphysin is a component of clathrin coats formed during synaptic vesicle recycling at the lamprey giant synapse","volume":"5","author":"Evergren","year":"2004","journal-title":"Traffic"},{"key":"2021111720203797900_B39","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/S0962-8924(02)02309-7","article-title":"The endocytic machinery at an interface with the actin cytoskeleton: a dynamic, hip intersection","volume":"12","author":"McPherson","year":"2002","journal-title":"Trends Cell Biol."},{"key":"2021111720203797900_B40","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/10091","article-title":"SH3-domain-containing proteins function at distinct steps in clathrin-coated vesicle formation","volume":"1","author":"Simpson","year":"1999","journal-title":"Nat. Cell Biol."},{"key":"2021111720203797900_B41","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.bbrc.2008.05.156","article-title":"Alternative splicing affecting the SH3A domain controls the binding properties of intersectin 1 in neurons","volume":"372","author":"Tsyba","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021111720203797900_B42","doi-asserted-by":"crossref","first-page":"3281","DOI":"10.1093\/hmg\/ddn224","article-title":"Mice deficient for the chromosome 21 ortholog Itsn1 exhibit vesicle-trafficking abnormalities","volume":"17","author":"Yu","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"2021111720203797900_B43","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/nn1002","article-title":"Actin has a molecular scaffolding, not propulsive, role in presynaptic function","volume":"6","author":"Sankaranarayanan","year":"2003","journal-title":"Nat. Neurosci."},{"key":"2021111720203797900_B44","doi-asserted-by":"crossref","first-page":"14476","DOI":"10.1073\/pnas.212381799","article-title":"Impaired recycling of synaptic vesicles after acute perturbation of the presynaptic actin cytoskeleton","volume":"99","author":"Shupliakov","year":"2002","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021111720203797900_B45","doi-asserted-by":"crossref","first-page":"382 e381","DOI":"10.1016\/j.cell.2009.04.012","article-title":"SnapShot: endocytic trafficking","volume":"137","author":"Wieffer","year":"2009","journal-title":"Cell"},{"key":"2021111720203797900_B46","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1091\/mbc.e02-08-0494","article-title":"Intersectin 1L guanine nucleotide exchange activity is regulated by adjacent src homology 3 domains that are also involved in endocytosis","volume":"14","author":"Zamanian","year":"2003","journal-title":"Mol. Biol. Cell"},{"key":"2021111720203797900_B47","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/ncb837","article-title":"Imaging actin and dynamin recruitment during invagination of single clathrin-coated pits","volume":"4","author":"Merrifield","year":"2002","journal-title":"Nat. Cell Biol."},{"key":"2021111720203797900_B48","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1078\/0171-9335-00356","article-title":"Neural Wiskott Aldrich syndrome protein (N-WASP) and the Arp2\/3 complex are recruited to sites of clathrin-mediated endocytosis in cultured fibroblasts","volume":"83","author":"Merrifield","year":"2004","journal-title":"Eur. J. Cell Biol."},{"key":"2021111720203797900_B49","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.bbrc.2006.10.169","article-title":"MNB\/DYRK1A phosphorylation regulates the interactions of synaptojanin 1 with endocytic accessory proteins","volume":"351","author":"Adayev","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021111720203797900_B50","first-page":"131","article-title":"Functional genomics of Down syndrome: a multidisciplinary approach","author":"Dierssen","year":"2001","journal-title":"J. Neural Transm. Suppl."},{"key":"2021111720203797900_B51","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S0002-9440(10)64538-5","article-title":"Endocytic pathway abnormalities precede amyloid \u03b2 deposition in sporadic Alzheimer's disease and Down syndrome: differential effects of APOE genotype and presenilin mutations","volume":"157","author":"Cataldo","year":"2000","journal-title":"Am. J. Pathol."},{"key":"2021111720203797900_B52","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1006\/geno.1996.0636","article-title":"Isolation of human and murine homologues of the Drosophila minibrain gene: human homologue maps to 21q22.2 in the Down syndrome \u2018critical region\u2019","volume":"38","author":"Song","year":"1996","journal-title":"Genomics"},{"key":"2021111720203797900_B53","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1006\/geno.1999.5775","article-title":"Human minibrain homologue (MNBH\/DYRK1): characterization, alternative splicing, differential tissue expression, and overexpression in Down syndrome","volume":"57","author":"Guimera","year":"1999","journal-title":"Genomics"},{"key":"2021111720203797900_B54","doi-asserted-by":"crossref","first-page":"10173","DOI":"10.1021\/bi036060+","article-title":"Mnb\/Dyrk1A phosphorylation regulates the interaction of dynamin 1 with SH3 domain-containing proteins","volume":"43","author":"Huang","year":"2004","journal-title":"Biochemistry"},{"key":"2021111720203797900_B55","doi-asserted-by":"crossref","first-page":"17597","DOI":"10.1074\/jbc.M111101200","article-title":"Dynamin is a minibrain kinase\/dual specificity Yak1-related kinase 1A substrate","volume":"277","author":"Chen-Hwang","year":"2002","journal-title":"J. Biol. Chem."}],"container-title":["Biochemical Society Transactions"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/38\/1\/181\/547114\/bst0380181.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/38\/1\/181\/547114\/bst0380181.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T00:02:23Z","timestamp":1637193743000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article\/38\/1\/181\/66086\/Intersectin-1-a-versatile-actor-in-the-synaptic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,1,19]]},"references-count":55,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2010,1,19]]},"published-print":{"date-parts":[[2010,2,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bst0380181","relation":{},"ISSN":["0300-5127","1470-8752"],"issn-type":[{"value":"0300-5127","type":"print"},{"value":"1470-8752","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,1,19]]}}}