The Protein Arginine Methyltransferase PRMT-5 Regulates SER-2 Tyramine Receptor-Mediated Behaviors in Caenorhabditis elegans.
The Protein Arginine Methyltransferase PRMT-5 Regulates SER-2 Tyramine Receptor-Mediated Behaviors in Caenorhabditis elegans.
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DOI：
10.1534/g3.118.200360
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发表时间：
2018-07-02
期刊：
影响因子：
--
通讯作者：
Ferkey DM
中科院分区：
文献类型：
--
作者：
Bowitch A;Michaels KL;Yu MC;Ferkey DM
G蛋白偶联受体是7次跨膜受体，其偶联至异源三聚体G蛋白以介导对多种刺激的细胞应答。了解调节G蛋白偶联受体的机制对于操纵其信号传导以获得治疗益处至关重要。一个关键的调节机制，有助于许多信号蛋白的功能多样性是翻译后修饰。而磷酸化仍然是最好的研究这种修饰，精氨酸甲基化的蛋白质精氨酸甲基转移酶正在成为一个关键的调节蛋白质功能。我们先前发表了第一个功能性证据，表明G蛋白偶联受体的精氨酸甲基化调节其信号传导。我们在这里报告的第三个受体，是由精氨酸甲基化，秀丽隐杆线虫SER-2酪胺受体。我们发现，在一个假定的甲基化基序在SER-2的第三个细胞内环内的丝氨酸甲基化的PRMT 5在体外。我们的数据还表明，这种修饰增强了体内SER-2信号传导以调节动物行为。第三个G蛋白偶联受体的鉴定表明，精氨酸甲基化在功能上受到调节，这种翻译后修饰可用于通过广泛的G蛋白偶联受体来调节信号传导。
G protein-coupled receptors are 7-pass transmembrane receptors that couple to heterotrimeric G proteins to mediate cellular responses to a diverse array of stimuli. Understanding the mechanisms that regulate G protein-coupled receptors is crucial to manipulating their signaling for therapeutic benefit. One key regulatory mechanism that contributes to the functional diversity of many signaling proteins is post-translational modification. Whereas phosphorylation remains the best studied of such modifications, arginine methylation by protein arginine methyltransferases is emerging as a key regulator of protein function. We previously published the first functional evidence that arginine methylation of G protein-coupled receptors modulates their signaling. We report here a third receptor that is regulated by arginine methylation, the Caenorhabditis elegans SER-2 tyramine receptor. We show that arginines within a putative methylation motif in the third intracellular loop of SER-2 are methylated by PRMT5 in vitro. Our data also suggest that this modification enhances SER-2 signaling in vivo to modulate animal behavior. The identification of a third G protein-coupled receptor to be functionally regulated by arginine methylation suggests that this post-translational modification may be utilized to regulate signaling through a broad array of G protein-coupled receptors.
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