Interaction of transmembrane AMPA receptor regulatory proteins with multiple membrane associated guanylate kinases

Interaction of transmembrane AMPA receptor regulatory proteins with multiple membrane associated guanylate kinases
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DOI:
10.1016/s0028-3908(03)00267-3
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发表时间:
2003-11-01
期刊:
影响因子:
4.7
通讯作者:
Bredt, DS
Bredt, DS
中科院分区:
医学2区
文献类型:
--
作者:
Dakoji, S;Tomita, S;Bredt, DS

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AMPA型谷氨酸受体的表面表达需要stargazin或相关的跨膜AMPA受体调节蛋白(TARP)。此外,TARPs的胞质尾部与PSD-95的PDZ结构域的相互作用将AMPA受体靶向突触后密度。在这里。我们筛选了可能与TARPs细胞质结构域相互作用的其他蛋白质。用酵母双杂交系统筛选大鼠脑cDNA文库,得到6个可以结合TARPs尾部的PDZ蛋白。这些PDZ蛋白包括4种神经元膜相关鸟苷酸激酶:PSD-95/SAP-90、PSD-93/Chapsyn-110、SAP-97/hDLG和SAP-102;multi-PDZ蛋白MUPP1;以及线粒体PDZ蛋白OMP-25。尽管所有这些蛋白在体外都能与TARPs结合,但其中只有PSD-95和PSD-93两种蛋白在脑内与TARPs结合。我们还发现PSD-95的所有三个PDZ结构域都与TARP c端具有相似的亲和力。这项工作在体外鉴定了TARP c -末端与PDZ结构域相互作用的生化混杂性,但也表明在大脑中只有特定的突触PDZ蛋白与TARPs相关联。(C) 2003 Elsevier Ltd.版权所有。
Surface expression of AMPA type glutamate, receptors requires stargazin or a related transmembrane AMPA receptor regulatory protein (TARP). Furthermore, interaction of the cytosolic tail of TARPs with PDZ domains of PSD-95 targets AMPA receptors to postsynaptic densities. Here. we screened for additional proteins that might interact with the cytosolic domain of TARPs. screening a rat brain cDNA library with the yeast two-hybrid system yielded six PDZ proteins that can bind tail of TARPs. These PDZ proteins include the four neuronal membrane associated guanylate kinases, PSD-95/SAP-90, PSD-93/Chapsyn-110, SAP-97/hDLG and SAP-102; the multi-PDZ protein, MUPP1; and the mitochondrial PDZ protein, OMP-25. Although all of these proteins can bind to TARPs in vitro, only two of these, PSD-95 and PSD-93 associate with TARPs in brain. We also found that all three PDZ domains from PSD-95 associate with the TARP C-termini with similar affinities. This work identifies biochemical promiscuity for interaction of the TARP C-termini with PDZ domains in vitro, but also shows that only specific synaptic PDZ proteins associate with TARPs in brain. (C) 2003 Elsevier Ltd. All rights reserved.