Evidence map›Paper›PMID 42722688›Full record

ArticleNature communications2026

Configurational diversity of metabotropic glutamate receptor complexes with beta-arrestins.

Dagan C Marx, Alberto J Gonzalez-Hernandez, Joon Lee, Dirk Siepe, Willem F Weber, Kevin Huynh, Pamela N Gallo, Sheida Sharghi Moshtaghin, Anisul Arefin, Johannes Broichhagen and 3 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Dagan C MarxDepartment of Biochemistry and Biophysics, Weill Cornell Medicine, New York, NY, USA.
Alberto J Gonzalez-HernandezDepartment of Biochemistry and Biophysics, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-2817-2475
Joon LeeDepartment of Biochemistry and Biophysics, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0003-3887-8540
Dirk SiepeDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-0009-8023
Willem F WeberDepartment of Biochemistry and Biophysics, Weill Cornell Medicine, New York, NY, USA.
Kevin HuynhDepartment of Biochemistry and Biophysics, Weill Cornell Medicine, New York, NY, USA.
Pamela N GalloDepartment of Biochemistry and Biophysics, Weill Cornell Medicine, New York, NY, USA.
Sheida Sharghi MoshtaghinDepartment of Biochemistry and Biophysics, Weill Cornell Medicine, New York, NY, USA.
Anisul ArefinDepartment of Biochemistry and Biophysics, Weill Cornell Medicine, New York, NY, USA.
Johannes BroichhagenLeibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany.ORCID http://orcid.org/0000-0003-3084-6595
Marian KalocsayDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-4187-5829
David EliezerDepartment of Biochemistry and Biophysics, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-1311-7537
Joshua LevitzDepartment of Biochemistry and Biophysics, Weill Cornell Medicine, New York, NY, USA. jtl2003@med.cornell.edu.ORCID http://orcid.org/0000-0002-8169-6323

Funding

Structure and Function of Protein Disorder in Membrane Trafficking and OrganizationR35GM136686 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI ELIEZER, DAVID · 2020 to 2025
$4.5M
Mechanisms of Regulation of Metabotropic Glutamate ReceptorsR01NS129904 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI Joshua Levitz · 2023 to 2026
$2.6M
Structure and function of mGluR3 interactions with beta-arrestins and the membrane.F32GM148001 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI MARX, DAGAN · 2022 to 2023
$137k
Structural and Allosteric Mechanisms of mGluR ActivationF31NS129320 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI STRAUSS, ALEXA · 2023 to 2024
$97k
NIGMS NIH HHS F32 GM148001NIGMS NIH HHS R35 GM136686NINDS NIH HHS F31 NS129320NINDS NIH HHS R01 NS129904
6 · The paper itself

Abstract

Beta-arrestins (β-arrs) are cytosolic proteins which mediate G protein-coupled receptor (GPCR) desensitization, endocytosis, and signaling. Despite the widespread physiological roles of β-arr coupling, the molecular basis of GPCR/β-arr interaction has been studied primarily in monomeric family A GPCRs. Here we develop a single molecule pulldown (SiMPull) assay that reports on both relative GPCR:β-arr interaction strength and stoichiometry to uncover molecular diversity in β-arr coupling to the neuromodulatory metabotropic glutamate receptors (mGluRs), prototypical, dimeric family C GPCRs. We find that mGluRs couple to β-arrs with variable apparent strength and a 2:1 or 2:2 stoichiometry. Focusing on the mGluR8/β-arr1 interaction, we map the contributions of "tail" and "core" interactions with residues in the receptor C-terminal domain and intracellular loops, respectively. Combinatorial mutagenesis enables the identification of a landscape of β-arr complexes with homo- and hetero-dimeric mGluR8, including both "cis" and "trans" interactions. Finally, we use our SiMPull assay in conjunction with live cell imaging and transcriptomic analysis to reveal that mGluRs can form megacomplexes either by simultaneously binding β-arr1 and β-arr2 or β-arr and G proteins. Together, this study provides a comprehensive framework for mGluR/β-arr complex diversity, expanding the known range of GPCR/transducer coupling modes.

Indexed as

beta-ArrestinsReceptors, Metabotropic GlutamateAnimalsHEK293 CellsHumansProtein BindingSignal Transductionbeta-Arrestinsmetabotropic glutamate receptor 8Receptors, Metabotropic Glutamate

Identifiers

PMID42722688
PMCPMC13562520

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.