Proteasomal-Mediated Degradation of AKAP150 Accompanies AMPAR Endocytosis during cLTD

The number and function of synaptic AMPA receptors (AMPARs) tightly regulates excitatory synaptic transmission. Current evidence suggests that AMPARs are inserted into the postsynaptic membrane during long-term potentiation (LTP) and are removed from the membrane during long-term depression (LTD). D...

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Detalles Bibliográficos
Autores: Cheng, Wenwen|||0000-0002-5462-8245, Siedlecki-Wullich, Dolores|||0000-0002-9099-9406, Català-Solsona, Judit|||0000-0002-2927-9135, Fábregas Ordóñez, Cristina, Fadó, Rut|||0000-0002-3293-2342, Casals, Nuria|||0000-0002-6719-4300, Solé Piñol, Montserrat|||0000-0003-4240-6562, Unzeta López, Mercedes|||0000-0002-7113-3383, Saura Antolín, Carlos|||0000-0003-3692-5657, Rodríguez Álvarez, José|||0000-0001-8582-8082, Miñano Molina, Alfredo Jesús|||0000-0002-7761-5682
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:227681
Acceso en línea:https://ddd.uab.cat/record/227681
https://dx.doi.org/urn:doi:10.1523/ENEURO.0218-19.2020
Access Level:acceso abierto
Palabra clave:AKAP150
AMPAR
LTD
LTP
Plasticity
Trafficking
Descripción
Sumario:The number and function of synaptic AMPA receptors (AMPARs) tightly regulates excitatory synaptic transmission. Current evidence suggests that AMPARs are inserted into the postsynaptic membrane during long-term potentiation (LTP) and are removed from the membrane during long-term depression (LTD). Dephosphorylation of GluA1 at Ser-845 and enhanced endocytosis are critical events in the modulation of LTD. Moreover, changes in scaffold proteins from the postsynaptic density (PSD) could be also related to AMPAR regulation in LTD. In the present study we analyzed the effect of chemical LTD (cLTD) on A-kinase anchoring protein (AKAP)150 and AMPARs levels in mouse-cultured neurons. We show that cLTD induces AKAP150 protein degradation via proteasome, coinciding with GluA1 dephosphorylation at Ser-845 and endocytosis of GluA1-containing AMPARs. Pharmacological inhibition of proteasome activity, but not phosphatase calcineurin (CaN), reverted cLTD-induced AKAP150 protein degradation. Importantly, AKAP150 silencing induced dephosphorylation of GluA1 Ser-845 and GluA1-AMPARs endocytosis while AKAP150 overexpression blocked cLTD-mediated GluA1-AMPARs endocytosis. Our results provide direct evidence that cLTD-induced AKAP150 degradation by the proteasome contributes to synaptic AMPARs endocytosis.

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