title: The AAA+ ATPase Thorase regulates AMPA receptor-dependent synaptic plasticity and behavior.
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.
authors.affiliation: Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhikai
authors.initials: Z
authors.lastname: Chi
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Keuss
authors.forename: Ying-Min Emily
authors.initials: YM
authors.lastname: Pai
authors.forename: Ho Chul
authors.initials: HC
authors.lastname: Kang
authors.forename: Joo-Ho
authors.initials: JH
authors.lastname: Shin
authors.forename: Artem
authors.initials: A
authors.lastname: Bugayenko
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Yulan
authors.initials: Y
authors.lastname: Xiong
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Pletnikov
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
authors.forename: Ted M
authors.initials: TM
authors.lastname: Dawson
authors.forename: Valina L
authors.initials: VL
authors.lastname: Dawson
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007858:Learning; D008297:Male; D008568:Memory; D051379:Mice; D008969:Molecular Sequence Data; D009473:Neuronal Plasticity; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D016415:Sequence Alignment; D013569:Synapses
chemical_list: D018091:Receptors, AMPA; D000251:Adenosine Triphosphatases; C558645:Atad1 protein, rat; D000074183:ATPases Associated with Diverse Cellular Activities