Defining the Homo- and Heterodimerization Propensities of Metabotropic Glutamate Receptors
Summary: 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 rela...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-05-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720305544 |
| _version_ | 1823994691367993344 |
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| author | Joon Lee Hermany Munguba Vanessa A. Gutzeit Melanie Kristt Jeremy S. Dittman Joshua Levitz |
| author_facet | Joon Lee Hermany Munguba Vanessa A. Gutzeit Melanie Kristt Jeremy S. Dittman Joshua Levitz |
| author_sort | Joon Lee |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-12-18T16:38:39Z |
| format | Article |
| id | doaj.art-691ed9260bcf43e7a93217f9b99781e7 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-18T16:38:39Z |
| publishDate | 2020-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-691ed9260bcf43e7a93217f9b99781e72022-12-21T21:01:16ZengElsevierCell Reports2211-12472020-05-01315Defining the Homo- and Heterodimerization Propensities of Metabotropic Glutamate ReceptorsJoon Lee0Hermany Munguba1Vanessa A. Gutzeit2Melanie Kristt3Jeremy S. Dittman4Joshua Levitz5Department of Biochemistry, Weill Cornell Medicine, New York, NY 10065, USADepartment of Biochemistry, Weill Cornell Medicine, New York, NY 10065, USANeuroscience Graduate Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USADepartment of Biochemistry, Weill Cornell Medicine, New York, NY 10065, USADepartment of Biochemistry, Weill Cornell Medicine, New York, NY 10065, USA; Physiology, Biophysics and Systems Biology Graduate Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USADepartment of Biochemistry, Weill Cornell Medicine, New York, NY 10065, USA; Physiology, Biophysics and Systems Biology Graduate Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA; Tri-Institutional PhD Program in Chemical Biology, New York, NY 10065, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124720305544Metabotropic Glutamate ReceptorG Protein-Coupled ReceptorNeuromodulationHeterodimerizationSingle cell RNA sequencingsingle molecule fluorescence |
| spellingShingle | Joon Lee Hermany Munguba Vanessa A. Gutzeit Melanie Kristt Jeremy S. Dittman Joshua Levitz Defining the Homo- and Heterodimerization Propensities of Metabotropic Glutamate Receptors Cell Reports Metabotropic Glutamate Receptor G Protein-Coupled Receptor Neuromodulation Heterodimerization Single cell RNA sequencing single molecule fluorescence |
| title | Defining the Homo- and Heterodimerization Propensities of Metabotropic Glutamate Receptors |
| title_full | Defining the Homo- and Heterodimerization Propensities of Metabotropic Glutamate Receptors |
| title_fullStr | Defining the Homo- and Heterodimerization Propensities of Metabotropic Glutamate Receptors |
| title_full_unstemmed | Defining the Homo- and Heterodimerization Propensities of Metabotropic Glutamate Receptors |
| title_short | Defining the Homo- and Heterodimerization Propensities of Metabotropic Glutamate Receptors |
| title_sort | defining the homo and heterodimerization propensities of metabotropic glutamate receptors |
| topic | Metabotropic Glutamate Receptor G Protein-Coupled Receptor Neuromodulation Heterodimerization Single cell RNA sequencing single molecule fluorescence |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720305544 |
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