TARPs differentially decorate AMPA receptors to specify neuropharmacology

被引:120
|
作者
Kato, Akihiko S. [1 ]
Gill, Martin B. [1 ]
Yu, Hong [1 ]
Nisenbaum, Eric S. [1 ]
Bredt, David S. [1 ]
机构
[1] Eli Lilly & Co, Lilly Res Labs, Dept Neurosci, Indianapolis, IN 46285 USA
关键词
2 DISTINCT MECHANISMS; GLUTAMATE RECEPTORS; SYNAPTIC PLASTICITY; REGULATORY PROTEINS; AUXILIARY SUBUNITS; BIPOLAR DISORDER; MOUSE STARGAZER; GAMMA-SUBUNIT; SCHIZOPHRENIA; FAMILY;
D O I
10.1016/j.tins.2010.02.004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Transmembrane AMPA receptor regulatory proteins (TARPs) are the first identified auxiliary subunits for a neurotransmitter-gated ion channel. Although initial studies found that stargazin, the prototypical TARP, principally chaperones AMPA receptors, subsequent research demonstrated that it also regulates AMPA receptor kinetics and synaptic waveforms. Recent studies have identified a diverse collection of TARP isoforms - types Ia, Ib II that distinctly regulate AMPA receptor trafficking, gating and neuropharmacology. These TARP isoforms are heterogeneously expressed in specific neuronal populations and can differentially sculpt synaptic transmission and plasticity. Whole-genome analyses also link multiple TARP loci to childhood epilepsy, schizophrenia and bipolar disorder. TARPs emerge as vital components of excitatory synapses that participate both in signal transduction and in neuropsychiatric disorders.
引用
收藏
页码:241 / 248
页数:8
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