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

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.

Pubmed ID: 21496646

Authors

  • Zhang J
  • Wang Y
  • Chi Z
  • Keuss MJ
  • Pai YM
  • Kang HC
  • Shin JH
  • Bugayenko A
  • Wang H
  • Xiong Y
  • Pletnikov MV
  • Mattson MP
  • Dawson TM
  • Dawson VL

Journal

Cell

Publication Data

April 15, 2011

Associated Grants

  • Agency: NIA NIH HHS, Id: AG029368
  • Agency: NIDA NIH HHS, Id: DA00266
  • Agency: NIDA NIH HHS, Id: P50 DA000266
  • Agency: NIDA NIH HHS, Id: P50 DA000266-40
  • Agency: NIA NIH HHS, Id: R01 AG029368
  • Agency: NIA NIH HHS, Id: R01 AG029368-04
  • Agency: Intramural NIH HHS, Id:

Mesh Terms

  • Adenosine Triphosphatases
  • Amino Acid Sequence
  • Animals
  • Brain
  • Cells, Cultured
  • Female
  • Gene Expression Profiling
  • Humans
  • Learning
  • Male
  • Memory
  • Mice
  • Molecular Sequence Data
  • Neuronal Plasticity
  • Rats
  • Receptors, AMPA
  • Sequence Alignment
  • Synapses