Interclass GPCR heteromerization affects localization and trafficking
| Autor: | Stuart C. Sealfon, Urjita H. Shah, Rudy Toneatti, Miguel Fribourg, Paul T. Arsenovic, Juan F. López-Giménez, Justin M. Saunders, Daniel E. Conway, Jong M. Shin, Deanna L. Benson, William G.M. Janssen, Javier González-Maeso, Carl R. Mayer |
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| Rok vydání: | 2020 |
| Předmět: |
Mice
129 Strain G protein Endosome Endosomes Receptors Metabotropic Glutamate Biochemistry Article 03 medical and health sciences 0302 clinical medicine Animals Humans Receptor Serotonin 5-HT2A Amino Acids Receptor Clozapine Molecular Biology 030304 developmental biology G protein-coupled receptor Mice Knockout 0303 health sciences Microscopy Confocal Mechanism (biology) Chemistry Cell Membrane Cell Biology Bridged Bicyclo Compounds Heterocyclic Cell biology Protein Transport HEK293 Cells Multiprotein Complexes Serotonin Antagonists Serotonin Protein Multimerization Metabotropic glutamate receptor 2 030217 neurology & neurosurgery Intracellular Signal Transduction |
| Zdroj: | Sci Signal Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | Membrane trafficking processes regulate G protein-coupled receptor (GPCR) activity. Although class A GPCRs are capable of activating G proteins in a monomeric form, they can also potentially assemble into functional GPCR heteromers. Here, we showed that the class A serotonin 5-HT(2A) receptors (5-HT(2A)R) affected the localization and trafficking of class C metabotropic glutamate receptor 2 (mGluR2) through a mechanism that required their assembly as heteromers in mammalian cells. In the absence of agonists, 5-HT(2A)R was primarily localized within intracellular compartments, and coexpression of 5-HT(2A)R with mGluR2 increased the intracellular distribution of the otherwise plasma membrane-localized mGluR2. Agonists for either 5-HT(2A)R or mGluR2 differentially affected trafficking through Rab5-positive endosomes in cells expressing each component of the 5-HT(2A)R-mGluR2 heterocomplex alone, or together. Additionally, overnight pharmacological 5-HT(2A)R blockade with clozapine, but not with M100907, decreased mGluR2 density through a mechanism that involved heteromerization between 5-HT(2A)R and mGluR2. Using TAT-tagged peptides and chimeric constructs that are unable to form the interclass 5-HT(2A)R-mGluR2 complex, we demonstrated that heteromerization was necessary for the 5-HT(2A)R-dependent effects on mGluR2 subcellular distribution. Expression of 5-HT(2A)R also augmented intracellular localization of mGluR2 in mouse frontal cortex pyramidal neurons. Together, our data suggest that GPCR heteromerization may itself represent a mechanism of receptor trafficking and sorting. |
| Databáze: | OpenAIRE |
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