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dc.creatorFernández-Chacón, Rafael 
dc.creatorShin, Ok-Ho 
dc.creatorKönigstorfer, Andreas 
dc.creatorMatos, Maria F. 
dc.creatorMeyer, Alexander C. 
dc.creatorGarcía, Jesús 
dc.creatorGerber, Stefan H. 
dc.creatorRizo, Josep 
dc.creatorSüdhof, Thomas C. 
dc.creatorRosenmund, Christian 
dc.date.accessioned2015-01-19T12:00:18Z
dc.date.available2015-01-19T12:00:18Z
dc.date.issued2002
dc.identifier.issn1529-2401es
dc.identifier.issn0270-6474es
dc.identifier.urihttp://hdl.handle.net/11441/17820
dc.description.abstractSynaptotagmin 1, a Ca2+ sensor for fast synaptic vesicle exocytosis, contains two C2 domains that form Ca2+ -dependent complexes with phospholipids. To examine the functional importance of Ca2+ binding to the C2A domain of synaptotagmin 1, we studied two C2A domain mutations, D232N and D238N, using recombinant proteins and knock-in mice. Both mutations severely decreased intrinsic Ca2+ binding and Ca2+ - dependent phospholipid binding by the isolated C2A domain. Both mutations, however, did not alter the apparent Ca2+ affinity of the double C2 domain fragment, although both decreased the tightness of the Ca2+ /phospholipid/double C2 domain complex. When introduced into the endogenous synaptotagmin 1 gene in mice, the D232N and D238N mutations had no apparent effect on morbidity and mortality and caused no detectable alteration in the Ca2+ -dependent properties of synaptotagmin 1. Electrophysiological recordings of cultured hippocampal neurons from knock-in mice revealed that neither mutation induced major changes in synaptic transmission. The D232N mutation, however, caused increased synaptic depression during repetitive stimulation, whereas the D238N mutation did not exhibit this phenotype. Our data indicate that Ca2+ binding to the C2A domain of synaptotagmin 1 may be important but not essential, consistent with the finding that the two C2 domains cooperate and may be partially redundant in Ca2+ - dependent phospholipid binding. Moreover, although the apparent Ca2+ affinity of the synaptotagmin 1/phospholipid complex is critical, the tightness of the Ca2+ /phospholipid complex is not. Our data also demonstrate that subtle changes in the biochemical properties of synaptotagmin 1 can result in significant alterations in synaptic responses.es
dc.language.isoenges
dc.relation.ispartofJournal of neuroscience, 22 (19), 8438-8446.es
dc.rightsAtribución-NoComercial-SinDerivadas 4.0 España*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectsynaptotagmines
dc.subjectneurotransmitter releasees
dc.subjectexocytosises
dc.subjectC2 domaines
dc.subjectCa2_-binding sitees
dc.subjectsynaptic plasticityes
dc.titleStructure/Function Analysis of Ca2 + Binding to the C2A Domain of Synaptotagmin 1es
dc.typeinfo:eu-repo/semantics/articlees
dcterms.identifierhttps://ror.org/03yxnpp24
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Fisiología Médica y Biofísicaes
dc.journaltitleJournal of neurosciencees
dc.publication.volumen22es
dc.publication.issue19es
dc.publication.initialPage8438es
dc.publication.endPage8446es
dc.identifier.idushttps://idus.us.es/xmlui/handle/11441/17820

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