{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T06:52:06Z","timestamp":1773989526336,"version":"3.50.1"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2017,9,27]],"date-time":"2017-09-27T00:00:00Z","timestamp":1506470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Foundation Directorate for Biological Sciences","award":["1257363"],"award-info":[{"award-number":["1257363"]}]},{"DOI":"10.13039\/100007235","name":"Colorado State University","doi-asserted-by":"publisher","award":["Libraries Open Access Research and Scholarship Fund"],"award-info":[{"award-number":["Libraries Open Access Research and Scholarship Fund"]}],"id":[{"id":"10.13039\/100007235","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007235","name":"Colorado State University","doi-asserted-by":"publisher","award":["Thornburg Graduate Research Excellence Award"],"award-info":[{"award-number":["Thornburg Graduate Research Excellence Award"]}],"id":[{"id":"10.13039\/100007235","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council UK","doi-asserted-by":"crossref","award":["G1002274, ID 98482"],"award-info":[{"award-number":["G1002274, ID 98482"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100011102","name":"European Union Seventh Framework Programme","doi-asserted-by":"crossref","award":["FP7\/2007-2013 305444 and 305121"],"award-info":[{"award-number":["FP7\/2007-2013 305444 and 305121"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council UK","doi-asserted-by":"crossref","award":["G1000848"],"award-info":[{"award-number":["G1000848"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["309548"],"award-info":[{"award-number":["309548"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wellcome Trust Investigator","award":["109915\/Z\/15\/Z"],"award-info":[{"award-number":["109915\/Z\/15\/Z"]}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR063634"],"award-info":[{"award-number":["R01AR063634"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0184817","type":"journal-article","created":{"date-parts":[[2017,9,27]],"date-time":"2017-09-27T17:38:47Z","timestamp":1506533927000},"page":"e0184817","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Drosophila studies support a role for a presynaptic synaptotagmin mutation in a human congenital myasthenic syndrome"],"prefix":"10.1371","volume":"12","author":[{"given":"Mallory C.","family":"Shields","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew R.","family":"Bowers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"McKenzie M.","family":"Fulcer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madelyn K.","family":"Bollig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick J.","family":"Rock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryan R.","family":"Sutton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alysia D.","family":"Vrailas-Mortimer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanns","family":"Lochm\u00fcller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger G.","family":"Whittaker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"Horvath","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1647-3166","authenticated-orcid":true,"given":"Noreen E.","family":"Reist","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2017,9,27]]},"reference":[{"issue":"4","key":"ref1","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/0896-6273(94)90342-5","article-title":"The effect on synaptic physiology of synaptotagmin mutations in Drosophila","volume":"12","author":"A DiAntonio","year":"1994","journal-title":"Neuron"},{"issue":"23","key":"ref2","doi-asserted-by":"crossref","first-page":"10888","DOI":"10.1073\/pnas.91.23.10888","article-title":"Calcium dependence of neurotransmitter release and rate of spontaneous vesicle fusions are altered in Drosophila synaptotagmin mutants","volume":"91","author":"JT Littleton","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"ref3","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/0092-8674(94)90556-8","article-title":"Synaptotagmin I: a major Ca2+ sensor for transmitter release at a central synapse","volume":"79","author":"M Geppert","year":"1994","journal-title":"Cell"},{"issue":"6895","key":"ref4","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/nature00846","article-title":"The C(2)B Ca(2+)-binding motif of synaptotagmin is required for synaptic transmission in vivo","volume":"418","author":"JM Mackler","year":"2002","journal-title":"Nature"},{"issue":"27","key":"ref5","first-page":"6127","article-title":"Synaptotagmin I synchronizes transmitter release in mouse hippocampal neurons. The Journal of neuroscience: the official journal of the","volume":"24","author":"T Nishiki","year":"2004","journal-title":"Society for Neuroscience"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1146\/annurev.biochem.77.062005.101135","article-title":"How does synaptotagmin trigger neurotransmitter release?","volume":"77","author":"ER Chapman","year":"2008","journal-title":"Annual review of biochemistry"},{"issue":"5059","key":"ref7","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1126\/science.1589771","article-title":"Synaptotagmin: a calcium sensor on the synaptic vesicle surface","volume":"256","author":"N Brose","year":"1992","journal-title":"Science (New York, NY)"},{"issue":"6","key":"ref8","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/0092-8674(95)90296-1","article-title":"Structure of the first C2 domain of synaptotagmin I: a novel Ca2+\/phospholipid-binding fold","volume":"80","author":"RB Sutton","year":"1995","journal-title":"Cell"},{"issue":"6","key":"ref9","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/S0896-6273(01)00548-7","article-title":"Three-dimensional structure of the synaptotagmin 1 C2B-domain: synaptotagmin 1 as a phospholipid binding machine","volume":"32","author":"I Fernandez","year":"2001","journal-title":"Neuron"},{"issue":"6895","key":"ref10","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/nature00915","article-title":"Synaptotagmins I and IV promote transmitter release independently of Ca(2+) binding in the C(2)A domain","volume":"418","author":"IM Robinson","year":"2002","journal-title":"Nature"},{"issue":"33","key":"ref11","doi-asserted-by":"crossref","first-page":"14869","DOI":"10.1073\/pnas.1000606107","article-title":"Differential regulation of synchronous versus asynchronous neurotransmitter release by the C2 domains of synaptotagmin 1","volume":"107","author":"M Yoshihara","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"ref12","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1523\/JNEUROSCI.4652-11.2012","article-title":"Calcium binding by synaptotagmin&apos;s C2A domain is an essential element of the electrostatic switch that triggers synchronous synaptic transmission","volume":"32","author":"AR Striegel","year":"2012","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"issue":"5669","key":"ref13","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1126\/science.1097196","article-title":"Reconstitution of Ca2+-regulated membrane fusion by synaptotagmin and SNAREs","volume":"304","author":"WC Tucker","year":"2004","journal-title":"Science (New York, NY)"},{"issue":"39","key":"ref14","doi-asserted-by":"crossref","first-page":"8542","DOI":"10.1523\/JNEUROSCI.2545-04.2004","article-title":"Dual roles of the C2B domain of synaptotagmin I in synchronizing Ca2+-dependent neurotransmitter release","volume":"24","author":"T Nishiki","year":"2004","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"issue":"6","key":"ref15","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1016\/0896-6273(94)90415-4","article-title":"Functional properties of multiple synaptotagmins in brain","volume":"13","author":"B Ullrich","year":"1994","journal-title":"Neuron"},{"issue":"7","key":"ref16","doi-asserted-by":"crossref","first-page":"4906","DOI":"10.1523\/JNEUROSCI.15-07-04906.1995","article-title":"Cellular localization of synaptotagmin I, II, and III mRNAs in the central nervous system and pituitary and adrenal glands of the rat","volume":"15","author":"B Marqueze","year":"1995","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"issue":"3","key":"ref17","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.ajhg.2014.08.007","article-title":"Synaptotagmin 2 mutations cause an autosomal-dominant form of lambert-eaton myasthenic syndrome and nonprogressive motor neuropathy","volume":"95","author":"DN Herrmann","year":"2014","journal-title":"American journal of human genetics"},{"issue":"22","key":"ref18","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1212\/WNL.0000000000002185","article-title":"Electrophysiologic features of SYT2 mutations causing a treatable neuromuscular syndrome","volume":"85","author":"RG Whittaker","year":"2015","journal-title":"Neurology"},{"issue":"3","key":"ref19","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1083\/jcb.147.3.589","article-title":"Crystal structure of the cytosolic C2A-C2B domains of synaptotagmin III. Implications for Ca(+2)-independent snare complex interaction","volume":"147","author":"RB Sutton","year":"1999","journal-title":"J Cell Biol"},{"issue":"10","key":"ref20","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1110\/ps.04832604","article-title":"Crystallographic identification of Ca2+ and Sr2+ coordination sites in synaptotagmin I C2B domain","volume":"13","author":"Y Cheng","year":"2004","journal-title":"Protein science: a publication of the Protein Society"},{"issue":"1","key":"ref21","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S0896-6273(00)81136-8","article-title":"A genome-wide search for synaptic vesicle cycle proteins in Drosophila","volume":"26","author":"TE Lloyd","year":"2000","journal-title":"Neuron"},{"issue":"2","key":"ref22","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1083\/jcb.200312054","article-title":"Synaptotagmins are trafficked to distinct subcellular domains including the postsynaptic compartment","volume":"166","author":"B Adolfsen","year":"2004","journal-title":"J Cell Biol"},{"issue":"4","key":"ref23","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1242\/dev.118.4.1077","article-title":"Expression of synaptotagmin in Drosophila reveals transport and localization of synaptic vesicles to the synapse","volume":"118","author":"JT Littleton","year":"1993","journal-title":"Development (Cambridge, England)"},{"issue":"11","key":"ref24","doi-asserted-by":"crossref","first-page":"4924","DOI":"10.1523\/JNEUROSCI.13-11-04924.1993","article-title":"Identification and characterization of Drosophila genes for synaptic vesicle proteins","volume":"13","author":"A DiAntonio","year":"1993","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"issue":"1","key":"ref25","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1002\/gene.10002","article-title":"Drosophila synaptotagmin I null mutants survive to early adulthood","volume":"31","author":"CA Loewen","year":"2001","journal-title":"Genesis (New York, NY: 2000)"},{"key":"ref26","unstructured":"Dodge FA, Rahamimoff R. Co-operative action of calcium ions in transmitter release at the neuromuscular junction."},{"issue":"6","key":"ref27","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1152\/jn.1983.50.6.1380","article-title":"Motor-unit discharge rates in maximal voluntary contractions of three human muscles","volume":"50","author":"F Bellemare","year":"1983","journal-title":"Journal of neurophysiology"},{"issue":"2","key":"ref28","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1177\/074873040001500208","article-title":"Differential control of morning and evening components in the activity rhythm of Drosophila melanogaster\u2014sex-specific differences suggest a different quality of activity","volume":"15","author":"C Helfrich-Forster","year":"2000","journal-title":"Journal of biological rhythms"},{"issue":"6","key":"ref29","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1177\/0748730414555183","article-title":"p38 MAP kinase regulates circadian rhythms in Drosophila","volume":"29","author":"AD Vrailas-Mortimer","year":"2014","journal-title":"Journal of biological rhythms"},{"issue":"5","key":"ref30","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.exger.2005.02.005","article-title":"Rapid iterative negative geotaxis (RING): a new method for assessing age-related locomotor decline in Drosophila","volume":"40","author":"JW Gargano","year":"2005","journal-title":"Experimental gerontology"},{"issue":"1","key":"ref31","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/cne.1049","article-title":"Mutations in the second C2 domain of synaptotagmin disrupt synaptic transmission at Drosophila neuromuscular junctions","volume":"436","author":"JM Mackler","year":"2001","journal-title":"The Journal of comparative neurology"},{"issue":"4","key":"ref32","first-page":"1670","article-title":"Identification of a human synaptotagmin-1 mutation that perturbs synaptic vesicle cycling","volume":"125","author":"K Baker","year":"2015","journal-title":"The Journal of clinical investigation"},{"issue":"3","key":"ref33","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1073\/pnas.032541099","article-title":"C2A activates a cryptic Ca(2+)-triggered membrane penetration activity within the C2B domain of synaptotagmin I","volume":"99","author":"J Bai","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"ref34","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/nsmb1056","article-title":"Close membrane-membrane proximity induced by Ca(2+)-dependent multivalent binding of synaptotagmin-1 to phospholipids","volume":"13","author":"D Arac","year":"2006","journal-title":"Nat Struct Mol Biol"},{"issue":"5828","key":"ref35","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1126\/science.1142614","article-title":"How synaptotagmin promotes membrane fusion","volume":"316","author":"S Martens","year":"2007","journal-title":"Science (New York, NY)"},{"issue":"4","key":"ref36","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.cell.2009.05.049","article-title":"Synaptotagmin-mediated bending of the target membrane is a critical step in Ca(2+)-regulated fusion","volume":"138","author":"E Hui","year":"2009","journal-title":"Cell"},{"issue":"6","key":"ref37","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1523\/JNEUROSCI.3153-09.2011","article-title":"Membrane penetration by synaptotagmin is required for coupling calcium binding to vesicle fusion in vivo","volume":"31","author":"BE Paddock","year":"2011","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"issue":"2","key":"ref38","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nn.3013","article-title":"Uncoupling the roles of synaptotagmin I during endo- and exocytosis of synaptic vesicles","volume":"15","author":"J Yao","year":"2011","journal-title":"Nature neuroscience"},{"issue":"6272","key":"ref39","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1038\/345260a0","article-title":"Phospholipid binding by a synaptic vesicle protein homologous to the regulatory region of protein kinase C","volume":"345","author":"MS Perin","year":"1990","journal-title":"Nature"},{"issue":"2","key":"ref40","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1113\/jphysiol.1968.sp008469","article-title":"The role of calcium in neuromuscular facilitation","volume":"195","author":"B Katz","year":"1968","journal-title":"The Journal of physiology"},{"issue":"7","key":"ref41","doi-asserted-by":"crossref","first-page":"a005702","DOI":"10.1101\/cshperspect.a005702","article-title":"Short-term presynaptic plasticity","volume":"4","author":"WG Regehr","year":"2012","journal-title":"Cold Spring Harbor perspectives in biology"},{"issue":"3","key":"ref42","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.neuron.2017.02.047","article-title":"The Mechanisms and Functions of Synaptic Facilitation","volume":"94","author":"SL Jackman","year":"2017","journal-title":"Neuron"},{"issue":"1","key":"ref43","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/S0021-9258(18)52479-0","article-title":"Structural and functional conservation of synaptotagmin (p65) in Drosophila and humans","volume":"266","author":"MS Perin","year":"1991","journal-title":"The Journal of biological chemistry"},{"issue":"7","key":"ref44","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1016\/0092-8674(93)90356-U","article-title":"Synaptic transmission persists in synaptotagmin mutants of Drosophila","volume":"73","author":"A DiAntonio","year":"1993","journal-title":"Cell"},{"issue":"4","key":"ref45","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1534\/genetics.166.4.1775","article-title":"Construction of transgenic Drosophila by using the site-specific integrase from phage phiC31","volume":"166","author":"AC Groth","year":"2004","journal-title":"Genetics"},{"issue":"9","key":"ref46","doi-asserted-by":"crossref","first-page":"3312","DOI":"10.1073\/pnas.0611511104","article-title":"An optimized transgenesis system for Drosophila using germ-line-specific phiC31 integrases","volume":"104","author":"J Bischof","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"ref47","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1242\/dev.118.2.401","article-title":"Targeted gene expression as a means of altering cell fates and generating dominant phenotypes","volume":"118","author":"AH Brand","year":"1993","journal-title":"Development (Cambridge, England)"},{"issue":"1","key":"ref48","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1046\/j.1471-4159.1994.63010041.x","article-title":"Neural specificity of elav expression: defining a Drosophila promoter for directing expression to the nervous system","volume":"63","author":"KM Yao","year":"1994","journal-title":"Journal of neurochemistry"},{"issue":"16","key":"ref49","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1002\/jcc.20289","article-title":"Scalable molecular dynamics with NAMD","volume":"26","author":"JC Phillips","year":"2005","journal-title":"Journal of computational chemistry"},{"issue":"2","key":"ref50","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1080\/01677060490894522","article-title":"A modified minimal hemolymph-like solution, HL3.1, for physiological recordings at the neuromuscular junctions of normal and mutant Drosophila larvae","volume":"18","author":"Y Feng","year":"2004","journal-title":"Journal of neurogenetics"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0184817","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T09:17:19Z","timestamp":1719479839000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0184817"}},"subtitle":[],"editor":[{"given":"Brian D.","family":"McCabe","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2017,9,27]]},"references-count":50,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2017,9,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0184817","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,27]]}}}