Details

Autor(en) / Beteiligte

• Citri, Ami
• Soler-Llavina, Gilberto
• Bhattacharyya, Samarjit
• Malenka, Robert C.

Titel

NMDAR- and mGluR-dependent long term depression are differentially regulated by the ubiquitin-proteasome system

Ist Teil von

• The European journal of neuroscience, 2009-10, Vol.30 (8), p.1443-1450

Erscheinungsjahr

2009

Quelle

EBSCOhost Psychology and Behavioral Sciences Collection

Beschreibungen/Notizen

• Long-term depression (LTD) in CA1 pyramidal neurons can be induced by activation of either NMDA receptors (NMDARs) or metabotropic glutamate receptors (mGluRs), both of which elicit changes in synaptic efficacy through AMPA receptor (AMPAR) endocytosis. To address the role of the ubiquitin-proteasome system in regulating AMPAR endocytosis during these forms of LTD, we examined the effects of pharmacological inhibitors of proteasomal degradation and protein ubiquitination on endocytosis of GluR1-containing AMPARs in dissociated rat hippocampal cultures as well as LTD of excitatory synaptic responses in acute rat hippocampal slices. Our findings suggest that the contribution of the ubiquitin-proteasome system to NMDAR-induced versus mGluR-induced AMPAR endocytosis and the consequent LTD differs significantly. NMDAR-induced AMPAR endocytosis and LTD occur independently of proteasome function, but appear to depend, at least in part, on ubiquitination. In contrast, mGluR-induced AMPAR endocytosis and LTD are enhanced by inhibition of proteasomal degradation, as well as by the inhibitor of protein ubiquitination. Furthermore, the decay of mGluR-induced membrane depolarization and Erk activation is delayed following inhibition of either ubiquitination or proteasomal degradation. These results suggest that while NMDAR-dependent LTD may utilize ubiquitin as a signal for AMPAR endocytosis, mGluR-induced signaling and LTD is limited by a feedback mechanism that involves the ubiquitin-proteasome system.