Distinct beta-arrestin coupling and intracellular trafficking of metabotropic glutamate receptor homo- and heterodimers.
Distinct beta-arrestin coupling and intracellular trafficking of metabotropic glutamate receptor homo- and heterodimers.
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DOI：
10.1126/sciadv.adi8076
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发表时间：
2023-12-08
期刊：
影响因子：
13.6
通讯作者：
Levitz, Joshua
中科院分区：
文献类型：
--
作者：
Lee, Joon;Gonzalez-Hernandez, Alberto J.;Kristt, Melanie;Abreu, Nohely;Rossmann, Kilian;Arefin, Anisul;Marx, Dagan C.;Broichhagen, Johannes;Levitz, Joshua
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. Homo- and hetero-dimeric mGluR complexes show diverse modes of regulation by beta-arrestins.
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影响因子：
5.6
作者：
Fang Z;Chen S;Manchanda Y;Bitsi S;Pickford P;David A;Shchepinova MM;Corrêa IR Jr;Hodson DJ;Broichhagen J;Tate EW;Reimann F;Salem V;Rutter GA;Tan T;Bloom SR;Tomas A;Jones B
通讯作者：
Jones B
影响因子：
13.8
作者：
Ellaithy A;Gonzalez-Maeso J;Logothetis DA;Levitz J
通讯作者：
Levitz J
影响因子：
48
作者：
Asher WB;Geggier P;Holsey MD;Gilmore GT;Pati AK;Meszaros J;Terry DS;Mathiasen S;Kaliszewski MJ;McCauley MD;Govindaraju A;Zhou Z;Harikumar KG;Jaqaman K;Miller LJ;Smith AW;Blanchard SC;Javitch JA
通讯作者：
Javitch JA
影响因子：
4
作者：
Chiechio, Santina;Nicoletti, Ferdinando
通讯作者：
Nicoletti, Ferdinando
影响因子：
64.8
作者：
Du, Juan;Wang, Dejian;Zhao, Qiang
通讯作者：
Zhao, Qiang