Proteasomal-Mediated Degradation of AKAP150 Accompanies AMPAR Endocytosis During CLTD

Overview

Journal eNeuro

Specialty Neurology

Date 2020 Mar 25

PMID 32205379

Citations 5

Authors

Wenwen Cheng

Dolores Siedlecki-Wullich

Judit Catala-Solsona

Cristina Fabregas

Rut Fado

Nuria Casals

Montse Sole

Mercedes Unzeta

Carlos A Saura

Jose Rodriguez-Alvarez

Alfredo J Minano-Molina

Affiliations

Soon will be listed here.

Abstract

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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