Defining the Homo- and Heterodimerization Propensities of Metabotropic Glutamate Receptors
Defining the Homo- and Heterodimerization Propensities of Metabotropic Glutamate Receptors
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DOI：
10.1016/j.celrep.2020.107605
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发表时间：
2020-05-05
期刊：
影响因子：
8.8
通讯作者：
Levitz, Joshua
中科院分区：
文献类型：
--
作者：
Lee, Joon;Munguba, Hermany;Levitz, Joshua
八种代谢型谷氨酸受体（mGluRs）在整个神经系统中起关键的调节作用。mGluR的分子多样性被认为通过异二聚体的形成而进一步扩大，但是mGluR亚型在细胞水平的共表达和异二聚体形成的相对倾向还不清楚。在这里，我们分析了单细胞RNA测序数据，发现皮质锥体细胞表达多种mGluR亚型，不同的受体组合具有不同的特征。然后，我们开发了定量的，基于荧光的测定，以确定跨组-I，-II和-III mGluRs的相对同源和异源二聚体倾向。我们发现在一些情况下，包括mGluR 2与mGluR 3，我们确认在额叶皮质使用原位RNA杂交和免疫共沉淀的异源二聚化的强烈偏好。总之，我们的研究结果支持mGluR异源二聚化的生物学相关性，并突出了大脑中mGluR群体的复杂景观。
The eight metabotropic glutamate receptors (mGluRs) serve critical modulatory roles throughout the nervous system. The molecular diversity of mGluRs is thought to be further expanded by the formation of heterodimers, but the co-expression of mGluR subtypes at the cellular level and the relative propensities of heterodimer formation are not well known. Here, we analyze single-cell RNA sequencing data and find that cortical pyramidal cells express multiple mGluR subtypes with distinct profiles for different receptor combinations. We then develop quantitative, fluorescence-based assays to define the relative homo- and heterodimer propensities across group-I, -II, and -III mGluRs. We find a strong preference for heterodimerization in a number of cases, including mGluR2 with mGluR3, which we confirm in frontal cortex using in situ RNA hybridization and co-immunoprecipitation. Together, our findings support the biological relevance of mGluR heterodimerization and highlight the complex landscape of mGluR populations in the brain.