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dc.contributor.authorDaSilva, L.L.*
dc.contributor.authorWall, M.J.*
dc.contributor.authorde Almeida, Luciana P.*
dc.contributor.authorWauters, S.C.*
dc.contributor.authorJanuario, Y.C.*
dc.contributor.authorMuller, Jurgen*
dc.contributor.authorCorrêa, Sonia A.L.*
dc.date.accessioned2016-05-09T13:59:28Z
dc.date.available2016-05-09T13:59:28Z
dc.date.issued2016-05-04
dc.identifier.citationDaSilva LL, Wall MJ, de Almeida LP, Wauters SC, Januario YC, Muller J and Correa SAL (2016) Activity-Regulated Cytoskeleton-Associated Protein Controls AMPAR Endocytosis through a Direct Interaction with Clathrin-Adaptor Protein 2. eNeuro. 3(3).en_US
dc.identifier.urihttp://hdl.handle.net/10454/8321
dc.descriptionYesen_US
dc.description.abstractThe activity-regulated cytoskeleton-associated (Arc) protein control synaptic strength by facilitating AMPA receptor (AMPAR) endocytosis. Here we demonstrate that Arc targets AMPAR to be internalized through a direct interaction with the clathrin-adaptor protein 2 (AP-2). We show that Arc overexpression overexpression in dissociated hippocampal neurons obtained from C57BL/6 mouse reduces the density of AMPAR GluA1 subunits at the cell surface and reduces the amplitude and rectification of AMPAR-mediated miniature-excitatory postsynaptic currents (mEPSC). Mutations of Arc, that prevent the AP-2 interaction reduce Arc-mediated endocytosis of GluA1 and abolish the reduction in AMPAR-mediated mEPSC amplitude and rectification. Depletion of the AP-2 subunit µ2 blocks the Arc-mediated reduction in mEPSC amplitude, effect that is restored by re-introducing µ2. The Arc/AP-2 interaction plays an important role in homeostatic synaptic scaling as the Arc-dependent decrease in mEPSC amplitude, induced by a chronic increase in neuronal activity, is inhibited by AP-2 depletion. This data provides a mechanism to explain how activity-dependent expression of Arc decisively controls the fate of AMPAR at the cell surface and modulates synaptic strength, via the direct interaction with the endocytic clathrin adaptor AP-2.en_US
dc.description.sponsorshipThis work was supported by the BBSRC_FAPPA BB/J02127X/1 and BBSRC-BB/H018344/1 to SALC and by the FAPESP_RCUK_FAPPA 2012/50147-5 and FAPESP_Young Investigator’s grant 2009/50650-6 to LLdS. SCW was a PhD Student supported be the BBSRC/GSK PhD-CASE Studentship, LPdA is a postdoc fellow supported by FAPESP, YCJ was supported by a FAPESP scientific initiation scholarship.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://dx.doi.org/10.1523/ENEURO.0144-15.2016en_US
dc.rights© 2016 DaSilva et al. Full-text reproduced in accordance with the publisher’s copyright policy. This work is licensed under a Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/).en_US
dc.subjectArc; AMPAR; Endocytosis; Clathrin-adaptor; AP-2en_US
dc.titleActivity-Regulated Cytoskeleton-Associated Protein Controls AMPAR Endocytosis through a Direct Interaction with Clathrin-Adaptor Protein 2en_US
dc.status.refereedYesen_US
dc.date.Accepted2016-04-18
dc.typeArticleen_US
dc.type.versionAccepted Manuscripten_US


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