The metabotropic glutamate receptors (mGluRs) are a class of G-protein-coupled receptor that undergo extensive interactions with scaffolding proteins, and this is intrinsic to their function as an important group of neuromodulators at glutamatergic synapses. The Caenorhabditis elegans nervous system expresses three metabotropic glutamate receptors, MGL-1, MGL-2 and MGL-3. Relatively little is known about how the function and signalling of these receptors is organised in C. elegans. To identify proteins that scaffold the MGL-1 receptor, we have conducted a yeast two-hybrid screen. Three of the interacting proteins, MPZ-1, NRFL-1 and PTP-1, displayed motifs characteristic of mammalian mGluR scaffolding proteins. Using cellular co-expression criterion, we show mpz-1 and ptp-1 exhibited overlapping expression patterns with subsets of mgl-1 neurons. This included neurones in the pharyngeal nervous system that control the feeding organ of the worm. The mGluR agonist L-CCG-I inhibits the activity of this network in wild-type worms, in an MGL-1 and dose-dependent manner. We utilised L-CCG-I to identify if MGL-1 function was disrupted in mutants with deletions in the mpz-1 gene. The mpz-1 mutants displayed a largely wild-type response to L-CCG-I, suggesting MGL-1 signalling is not overtly disrupted consistent with a non-obligatory modulatory function in receptor scaffolding. The selectivity of the protein interactions and overlapping expression identified here warrant further investigation of the functional significance of scaffolding of metabotropic glutamate receptor function.

代谢型谷氨酸受体 (mGluR) 是一类 G 蛋白偶联受体，与支架蛋白发生广泛的相互作用，这是它们作为谷氨酸能突触中一组重要的神经调节剂的功能所固有的。秀丽隐杆线虫神经系统表达三种代谢型谷氨酸受体：MGL-1、MGL-2 和 MGL-3。关于线虫中这些受体的功能和信号传导是如何组织的，人们知之甚少。为了鉴定 MGL-1 受体支架的蛋白质，我们进行了酵母双杂交筛选。三种相互作用的蛋白 MPZ-1、NRFL-1 和 PTP-1 显示出哺乳动物 mGluR 支架蛋白的基序特征。使用细胞共表达标准，我们发现mpz - 1和ptp - 1与mgl - 1神经元子集表现出重叠的表达模式。这包括控制线虫进食器官的咽神经系统中的神经元。 mGluR 激动剂 L-CCG-I 以 MGL-1 和剂量依赖性方式抑制野生型蠕虫中该网络的活性。我们利用 L-CCG-I 来鉴定mpz - 1基因缺失的突变体中 MGL-1 功能是否被破坏。 mpz - 1突变体对L-CCG-I表现出很大程度上野生型的反应，表明MGL-1信号传导没有被明显破坏，这与受体支架中的非强制性调节功能一致。这里确定的蛋白质相互作用和重叠表达的选择性需要进一步研究代谢型谷氨酸受体功能支架的功能意义。