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

Jianmin Zhang, 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

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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.

Original languageEnglish (US)
Pages (from-to)284-299
Number of pages16
JournalCell
Volume145
Issue number2
DOIs
StatePublished - Apr 15 2011

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Zhang, J., Wang, Y., Chi, Z., Keuss, M. J., Pai, Y. M. E., Kang, H. C., Shin, J. H., Bugayenko, A., Wang, H., Xiong, Y., Pletnikov, M. V., Mattson, M. P., Dawson, T. M., & Dawson, V. L. (2011). The AAA+ ATPase Thorase regulates AMPA receptor-dependent synaptic plasticity and behavior. Cell, 145(2), 284-299. https://doi.org/10.1016/j.cell.2011.03.016