Literature DB >> 21496646

The AAA+ ATPase Thorase regulates AMPA receptor-dependent synaptic plasticity and behavior.

Jianmin Zhang1, Yue Wang, Zhikai Chi, Matthew J Keuss, Ying-Min Emily Pai, Ho Chul Kang, Joo-Ho Shin, Artem Bugayenko, Hong Wang, Yulan Xiong, Mikhail V Pletnikov, Mark P Mattson, Ted M Dawson, Valina L Dawson.   

Abstract

The synaptic insertion or removal of AMPA receptors (AMPAR) plays critical roles in the regulation of synaptic activity reflected in the expression of long-term potentiation (LTP) and long-term depression (LTD). The cellular events underlying this important process in learning and memory are still being revealed. Here we describe and characterize the AAA+ ATPase Thorase, which regulates the expression of surface AMPAR. In an ATPase-dependent manner Thorase mediates the internalization of AMPAR by disassembling the AMPAR-GRIP1 complex. Following genetic deletion of Thorase, the internalization of AMPAR is substantially reduced, leading to increased amplitudes of miniature excitatory postsynaptic currents, enhancement of LTP, and elimination of LTD. These molecular events are expressed as deficits in learning and memory in Thorase null mice. This study identifies an AAA+ ATPase that plays a critical role in regulating the surface expression of AMPAR and thereby regulates synaptic plasticity and learning and memory.
Copyright © 2011 Elsevier Inc. All rights reserved.

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Year:  2011        PMID: 21496646      PMCID: PMC3085003          DOI: 10.1016/j.cell.2011.03.016

Source DB:  PubMed          Journal:  Cell        ISSN: 0092-8674            Impact factor:   41.582


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