In:
European Journal of Neuroscience, Wiley, Vol. 30, No. 8 ( 2009-10), p. 1443-1450
Abstract:
Long‐term depression (LTD) in CA1 pyramidal neurons can be induced by activation of either N ‐methyl‐ d ‐aspartate receptors (NMDARs) or metabotropic glutamate receptors (mGluRs), both of which elicit changes in synaptic efficacy through α‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazole‐propionate 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 glutamate receptor 1 (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 vs. 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, although NMDAR‐dependent LTD may utilize ubiquitin as a signal for AMPAR endocytosis, mGluR‐induced signaling and LTD are limited by a feedback mechanism that involves the ubiquitin‐proteasome system.
Type of Medium:
Online Resource
ISSN:
0953-816X
,
1460-9568
DOI:
10.1111/ejn.2009.30.issue-8
DOI:
10.1111/j.1460-9568.2009.06950.x
Language:
English
Publisher:
Wiley
Publication Date:
2009
detail.hit.zdb_id:
2005178-5
SSG:
12
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