학술논문

Distinct beta-arrestin coupling and intracellular trafficking of metabotropic glutamate receptor homoand heterodimers.
Document Type
Article
Source
Science Advances. 12/8/2023, Vol. 9 Issue 49, p1-19. 19p.
Subject
*GLUTAMATE receptors
*ARRESTINS
*G protein coupled receptors
*HETERODIMERS
*NEURAL transmission
Language
ISSN
2375-2548
Abstract
The metabotropic glutamate receptors (mGluRs) are family C, dimeric G protein-coupled receptors (GPCRs), which play critical roles in synaptic transmission. Despite an increasing appreciation of the molecular diversity of this family, how distinct mGluR subtypes are regulated remains poorly understood. We reveal that different group II/III mGluR subtypes show markedly different beta-arrestin (β-arr) coupling and endocytic trafficking. While mGluR2 is resistant to internalization and mGluR3 shows transient β-arr coupling, which enables endocytosis and recycling, mGluR8 and β-arr form stable complexes, which leads to efficient lysosomal targeting and degradation. Using chimeras and mutagenesis, we pinpoint carboxyl-terminal domain regions that control β-arr coupling and trafficking, including the identification of an mGluR8 splice variant with impaired internalization. We then use a battery of high-resolution fluorescence assays to find that heterodimerization further expands the diversity of mGluR regulation. Together, this work provides insight into the relationship between GPCR/β-arr complex formation and trafficking while revealing diversity and intricacy in the regulation of mGluRs. [ABSTRACT FROM AUTHOR]