Group I Metabotropic Glutamate Receptors Bind to Protein Phosphatase 1C
Group I Metabotropic Glutamate Receptors Bind to Protein Phosphatase 1C
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I 组代谢型谷氨酸受体与蛋白磷酸酶 1C 结合
DOI：
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发表时间：
2003
影响因子：
4.8
通讯作者：
R. Enz
中科院分区：
文献类型：
--
作者：
C. Croci;H. Sticht;J. Brandstätter;R. Enz
蛋白激酶和磷酸酶对神经递质受体的调节是控制突触信号转导的关键机制。然而，参与这些酶的特定靶向和相互作用的分子决定因素在很大程度上是未知的。在这里，我们使用重组和天然蛋白制备，通过下拉试验和重组蛋白制备，在酵母细胞中鉴定了蛋白磷酸酶1C的两种催化γ异构体(pp1γ1和pp1γ2)为I组代谢型谷氨酸受体1a、5a和5b的结合伙伴。比较相互作用蛋白的组织分布，并在表达各自相互作用的谷氨酸受体的视网膜双极细胞的树突中检测到蛋白磷酸酶1C。我们绘制了结合伙伴内的相互作用结构域，并确定了代谢型谷氨酸受体1a、5a、5b和7b的胞内C末端的5个氨基酸是与蛋白磷酸酶1C结合的必要条件和充分条件。此外，我们还发现这些C末端在结合酶方面存在剂量依赖性的竞争。基于我们的数据，我们通过基于同源的分子模拟研究了与蛋白磷酸酶1C结合的氨基酸的结构。综上所述，这些结果提供了蛋白磷酸酶1C和代谢型谷氨酸受体之间相互作用的分子描述，从而增加了我们对谷氨酸能信号转导的理解。
The modulation of neurotransmitter receptors by kinases and phosphatases represents a key mechanism in controlling synaptic signal transduction. However, molecular determinants involved in the specific targeting and interactions of these enzymes are largely unknown. Here, we identified both catalytic γ-isoforms of protein phosphatase 1C (PP1γ1 and PP1γ2) as binding partners of the group I metabotropic glutamate receptors type 1a, 5a, and 5b in yeast cells and pull-down assays, using recombinant and native protein preparations. The tissue distribution of interacting proteins was compared, and protein phosphatase 1C was detected in dendrites of retinal bipolar cells expressing the respective interacting glutamate receptors. We mapped interacting domains within binding partners and identified five amino acids in the intracellular C termini of the metabotropic glutamate receptors type 1a, 5a, 5b, and 7b being both necessary and sufficient to bind protein phosphatase 1C. Furthermore, we show a dose-dependent competition of these C termini in binding the enzyme. Based on our data, we investigated the structure of the identified amino acids bound to protein phosphatase 1C by homology-based molecular modeling. In summary, these results provide a molecular description of the interaction between protein phosphatase 1C and metabotropic glutamate receptors and thereby increase our understanding of glutamatergic signal transduction.
DOI：
10.1016/s0021-9258(17)36713-3
发表时间：
1994-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Z. Zhang;S. Zhao;G. Bai;E. Y. Lee
通讯作者：
Z. Zhang;S. Zhao;G. Bai;E. Y. Lee