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dc.contributorUniversidad de Sevilla. Departamento de Fisiología Médica y Biofísicaes
dc.creatorGómez Scholl, Francisco Manuel es
dc.creatorServián Morilla, Emilia es
dc.creatorSaura, Carlos A. es
dc.date.accessioned2014-11-27T12:29:58Z
dc.date.available2014-11-27T12:29:58Z
dc.date.issued2011es
dc.identifier.citationGómez Scholl, F.M., Servián Morilla, E. y Saura, C.A. (2011). Presenilin/gamma-secretase regulates neurexin processing at synapses. PLoS One, 6 (4), e19430-1-e19430-13.
dc.identifier.issn1932-6203es
dc.identifier.otherhttp://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0019430&representation=PDFes
dc.identifier.urihttp://hdl.handle.net/11441/16685
dc.description.abstractNeurexins are a large family of neuronal plasma membrane proteins, which function as trans-synaptic receptors during synaptic differentiation. The binding of presynaptic neurexins to postsynaptic partners, such as neuroligins, has been proposed to participate in a signaling pathway that regulates synapse formation/stabilization. The identification of mutations in neurexin genes associated with autism and mental retardation suggests that dysfunction of neurexins may underlie synaptic defects associated with brain disorders. However, the mechanisms that regulate neurexin function at synapses are still unclear. Here, we show that neurexins are proteolytically processed by presenilins (PS), the catalytic components of the c-secretase complex that mediates the intramembraneous cleavage of several type I membrane proteins. Inhibition of PS/c-secretase by using pharmacological and genetic approaches induces a drastic accumulation of neurexin C-terminal fragments (CTFs) in cultured rat hippocampal neurons and mouse brain. Neurexin-CTFs accumulate mainly at the presynaptic terminals of PS conditional double knockout (PS cDKO) mice lacking both PS genes in glutamatergic neurons of the forebrain. The fact that loss of PS function enhances neurexin accumulation at glutamatergic terminals mediated by neuroligin-1 suggests that PS regulate the processing of neurexins at glutamatergic synapses. Interestingly, presenilin 1 (PS1) is recruited to glutamatergic terminals mediated by neuroligin-1, thus concentrating PS1 at terminals containing b-neurexins. Furthermore, familial Alzheimer’s disease (FAD)-linked PS1 mutations differentially affect b-neurexin-1 processing. Expression of PS1 M146L and PS1 H163R mutants in PS2/2 cells rescues the processing of bneurexin-1, whereas PS1 C410Y and PS1 DE9 fail to rescue the processing defect. These results suggest that PS regulate the synaptic function and processing of neurexins at glutamatergic synapses, and that impaired neurexin processing by PS may play a role in FAD.es
dc.language.isoengspa
dc.relation.ispartofPLoS One, 6 (4), e19430-1-e19430-13.es
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.titlePresenilin/gamma-secretase regulates neurexin processing at synapseses
dc.typeinfo:eu-repo/semantics/article
dcterms.identifierhttps://ror.org/03yxnpp24
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.journaltitlePLoS Onees
dc.publication.volumen6es
dc.publication.issue4es
dc.publication.initialPagee19430-1es
dc.publication.endPagee19430-13es
dc.identifier.idushttps://idus.us.es/xmlui/handle/11441/16685

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