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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Activity-Regulated Cytoskeleton- Associated Protein Controls AMPAR Endocytosis through a Direct Interaction with Clathrin-Adaptor Protein 2

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Autor(es):
DaSilva, Luis L. P. ; Wall, Mark J. ; de Almeida, Luciana P. ; Wauters, Sandrine C. ; Januario, Yunan C. ; Muller, Jurgen ; Correa, Sonia A. L.
Número total de Autores: 7
Tipo de documento: Artigo Científico
Fonte: ENEURO; v. 3, n. 3 MAY-JUN 2016.
Citações Web of Science: 9
Resumo

The activity-regulated cytoskeleton-associated (Arc) protein controls 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 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-EPSCs (mEPSCs). 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 mu 2 blocks the Arc-mediated reduction in mEPSC amplitude, an effect that is restored by reintroducing mu 2. 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. These data provide 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. (AU)

Processo FAPESP: 12/50147-5 - Role of endosomal sorting machinery controlling AMPA receptors trafficking in the hippocampus
Beneficiário:Luis Lamberti Pinto da Silva
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 09/50650-6 - Elucidação de mecanismos celulares e moleculares da modulação negativa de proteínas da superfície celular por NEF do HIV-1
Beneficiário:Luis Lamberti Pinto da Silva
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores