The PDZ proteins PICK1, GRIP, and syntenin bind multiple glutamate receptor subtypes - Analysis of PDZ binding motifs
The PDZ proteins PICK1, GRIP, and syntenin bind multiple glutamate receptor subtypes - Analysis of PDZ binding motifs
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DOI：
10.1074/jbc.c200112200
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发表时间：
2002-05-03
影响因子：
4.8
通讯作者：
Dev, KK
中科院分区：
文献类型：
--
作者：
Hirbec, H;Perestenko, O;Dev, KK
使用序列同源性搜索，酵母双杂交试验和谷胱甘肽S-转移酶（GST）下拉的方法，我们已经确定了一系列的谷氨酸受体亚基，与PDZ蛋白GRIP，PICK 1和syntenin的差异相互作用。GST下拉实验确定了更多的相互作用比酵母双杂交检测。我们报告了几种受体-蛋白质相互作用，强的包括：W GRIP和syntenin与mGluR 7a，mGluR 4a和mGluR 6;（ii）PICK 1和GRIP与mGluR 3;和（iii）syntenin与所有形式的GluR 1 -4和mGluR 7 b。我们进一步表征了在酵母双杂交和GST-下拉测定中发现的新型mGluR 7a-GRIP相互作用，并观察到mGluR 7a定位与海马神经元中的GRIP重叠。PICK 1、GRIP和syntenin的广泛靶点表明，它们可能代表了一种分子机制，可以在突触上的一个共同位点集中和/或调节许多不同的受体。这些数据还表明，PDZ相互作用中涉及的结构决定因素比最初设想的更复杂。
Using sequence homology searches, yeast two-hybrid assays and glutathione S-transferase (GST)-pull-down approaches we have identified a series of glutamate receptor subunits that interact differentially with the PDZ proteins GRIP, PICK1, and syntenin. GST-pull-down experiments identified more interactions than detected by yeast two-hybrid assays. We report several receptor-protein interactions, strong ones include: W GRIP and syntenin with mGluR7a, mGluR4a, and mGluR6; (ii) PICK1 and GRIP with mGluR3; and (iii) syntenin with all forms of GluR1-4 and mGluR7b. We further characterized the novel mGluR7a-GRIP interaction found both in yeast two-hybrid and GST-pull-down assays and observed that mGluR7a localization overlapped with GRIP with in hippocampal neurons. The wide range of targets for PICK1, GRIP, and syntenin suggests they may represent a molecular mechanism that can concentrate and/or regulate a number of different receptors at a common site on a synapse. These data also suggest that the structural determinants involved in PDZ interactions are more complex than originally envisaged.