A novel association of mGluR1a with the PDZ scaffold protein CAL modulates receptor activity-猫眼课题宝

DOI：

10.1016/j.febslet.2008.10.054

发表时间：

2008-12

期刊：

FEBS Letters

影响因子：

3.5

通讯作者：

中科院分区：

生物学3区

文献类型：

作者：

Jiuqin Zhang;Shan Cheng;Ying Xiong;Yanmei Ma;D. Luo;A. Jeromin;Hong Zhang;Junqi He

代谢型谷氨酸受体亚型 1a (mGluR1a) 与介导其受体活性的蛋白质相关，表明 mGluR1a 具有复杂控制的功能。在这里，通过体外和体内谷胱甘肽-S-转移酶下拉、免疫共沉淀和免疫荧光测定，我们发现 CFTR 相关配体 (CAL) 通过其 PSD95/discslarge/ZO1 同源结构域成为 mGluR1a 的新型结合伴侣。 mGluR1a 羧基末端 (CT) 的缺失或 mGluR1a CT 中 Leu 突变为 Ala 会降低这种关联，表明 mGluR1a 与 CAL 的重要结合区域。在功能上，mGluR1a 与 CAL 的相互作用被证明可以通过 C 端截短的受体抑制 mGluR1a 介导的 ERK1/2 激活，但没有明显的效果。这些发现可能为通过与 CAL 相互作用来调节 mGluR1a 介导的信号传导提供一种新机制。结构摘要：

Metabotropic glutamate receptor subtype 1a (mGluR1a) associates with the proteins mediating its receptor activity, suggesting a complex-controlled function of mGluR1a. Here, using glutathione-S-transferase pull-down, co-immnoprecipitation and immnoflurescence assays in vitro and in vivo, we have found CFTR-associated ligand (CAL) to be a novel binding partner of mGluR1a, through its PSD95/discslarge/ZO1homology domain. Deletion of mGluR1a-carboxyl terminus (CT) or mutation of Leu to Ala in the CT of mGluR1a reduces the association, indicating the essential binding region of mGluR1a for CAL. Functionally, the interaction of mGluR1a with CAL was shown to inhibit mGluR1a-mediated ERK1/2 activation, without an apparent effect, via the C-terminal-truncated receptor. These findings might provide a novel mechanism for the regulation of mGluR1a-mediated signaling through the interaction with CAL. STRUCTURED SUMMARY:

A novel association of mGluR1a with the PDZ scaffold protein CAL modulates receptor activity

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