Evidence map›Paper›PMID 27641494›Full record

ArticleNeuron2016

Mechanism of Assembly and Cooperativity of Homomeric and Heteromeric Metabotropic Glutamate Receptors.

Joshua Levitz, Chris Habrian, Shashank Bharill, Zhu Fu, Reza Vafabakhsh, Ehud Y Isacoff

Abstract read
In one paragraph

Article in Neuron, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
102citing papers in PubMed, 1 pooled it
–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

102 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Molecular pharmacology of mGluMolecular pharmacology · 2026
    Article
  5. No evidence for direct physical interaction of 5-HTbioRxiv : the preprint server for biology · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Profiling the Impact of mGluACS chemical neuroscience · 2025
    Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

42 more citing papers are in PubMed but not listed here.

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

6 authors.

Joshua LevitzDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA; Biophysics Graduate Group, University of California, Berkeley, CA 94720, USA.
Chris HabrianDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA; Biophysics Graduate Group, University of California, Berkeley, CA 94720, USA.
Shashank BharillDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Zhu FuDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Reza VafabakhshDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Ehud Y IsacoffDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA; Biophysics Graduate Group, University of California, Berkeley, CA 94720, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA; Bioscience Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: ehud@berkeley.edu.

Funding

NDC for the Optical Control of Biological FunctionPN2EY018241 · NEI · UNIVERSITY OF CALIFORNIA BERKELEY · PI ISACOFF, EHUD · 2006 to 2015
$37.5M
MOLECULAR BIOPHYSICS TRAINING GRANTT32GM008295 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI HURLEY, JAMES H, WEMMER, DAVID E · 1989 to 2022
$8.1M
Voltage Gating MechanismsR01GM117051 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI ISACOFF, EHUD · 2016 to 2019
$1.3M
Optical Stimulation MicroscopeS10RR028971 · NCRR · UNIVERSITY OF CALIFORNIA BERKELEY · PI ISACOFF, EHUD · 2011 to 2011
$596k
NCRR NIH HHS S10 RR028971NEI NIH HHS PN2 EY018241NIGMS NIH HHS R01 GM117051NIGMS NIH HHS T32 GM008295
6 · The paper itself

Abstract

G protein-coupled receptors (GPCRs) mediate cellular responses to a wide variety of extracellular stimuli. GPCR dimerization may expand signaling diversity and tune functionality, but little is known about the mechanisms of subunit assembly and interaction or the signaling properties of heteromers. Using single-molecule subunit counting on class C metabotropic glutamate receptors (mGluRs), we map dimerization determinants and define a heterodimerization profile. Intersubunit fluorescence resonance energy transfer measurements reveal that interactions between ligand-binding domains control the conformational rearrangements underlying receptor activation. Selective liganding with photoswitchable tethered agonists conjugated to one or both subunits of covalently linked mGluR2 homodimers reveals that receptor activation is highly cooperative. Strikingly, this cooperativity is asymmetric in mGluR2/mGluR3 heterodimers. Our results lead to a model of cooperative activation of mGluRs that provides a framework for understanding how class C GPCRs couple extracellular binding to dimer reorganization and G protein activation.

Indexed as

Protein Interaction Domains and MotifsProtein MultimerizationAnimalsCells, CulturedExcitatory Amino Acid AgonistsHumansMembrane PotentialsMutationOocytesProtein Structure, QuaternaryProtein SubunitsRatsReceptors, Metabotropic GlutamateXenopusExcitatory Amino Acid Agonistsmetabotropic glutamate receptor 2metabotropic glutamate receptor 3Protein SubunitsReceptors, Metabotropic Glutamate

Identifiers

PMID27641494
PMCPMC5053906

What OpenQuestion holds

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Registered trials

None linked

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.