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The AAA+ ATPase Thorase regulates AMPA receptor-dependent synaptic plasticity and behavior |
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| Authors: | Zhang Jianmin Wang Yue Chi Zhikai Keuss Matthew J Pai Ying-Min Emily Kang Ho Chul Shin Joo-Ho Bugayenko Artem Wang Hong Xiong Yulan Pletnikov Mikhail V Mattson Mark P Dawson Ted M Dawson Valina L |
| Institution: | 1 Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 2 Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 3 Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 4 Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 5 Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 6 Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21205, USA 7 Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA |
| 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. |
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