Evidence map›Paper›PMID 30428326›Full record

ArticleiScience2018

A Comprehensive Mutagenesis Screen of the Adhesion GPCR Latrophilin-1/ADGRL1.

Olha Nazarko, Amanuel Kibrom, Jana Winkler, Katherine Leon, Hannah Stoveken, Gabriel Salzman, Katarzyna Merdas, Yue Lu, Pradnya Narkhede, Gregory Tall and 2 more

Open access · goldAbstract read
In one paragraph

Article in iScience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
2.5field-weighted citation impact, top 10% of its field
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

41 citing papers in PubMed, 66 citations in OpenAlex.

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  13. Cell Adhesion Molecule Signaling at the Synapse: Beyond the Scaffold.Cold Spring Harbor perspectives in biology · 2024
    Review
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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

12 authors at 3 institutions in 2 countries.

Olha NazarkoDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.
Amanuel KibromDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.
Jana WinklerRudolf Schönheimer Institute of Biochemistry, Molecular Biochemistry, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany.
Katherine LeonDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.
Hannah StovekenDepartment of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
Gabriel SalzmanDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.
Katarzyna MerdasDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.
Yue LuDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.
Pradnya NarkhedeDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.
Gregory TallDepartment of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
Simone PrömelRudolf Schönheimer Institute of Biochemistry, Molecular Biochemistry, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany.
Demet AraçDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA; Grossman Institute for Neuroscience, Quantitative Biology and Human Behavior, The University of Chicago, Chicago, IL 60637, USA. Electronic address: arac@uchicago.edu.
University of Chicago · USLeipzig University · DEUniversity of Michigan · US

Funding

Molecular And Cellular Biology Training ProgramT32GM007183 · NIGMS · UNIVERSITY OF CHICAGO · PI GLICK, BENJAMIN S, RICE, PHOEBE A · 1985 to 2021
$23.9M
Structural and Functional Studies of Adhesion GPCRsR01GM120322 · NIGMS · UNIVERSITY OF CHICAGO · PI ARAC-OZKAN, DEMET · 2016 to 2020
$1.7M
Modulation and molecular mechanisms of GPR56 functionF30GM116455 · NIGMS · UNIVERSITY OF CHICAGO · PI SALZMAN, GABRIEL · 2015 to 2017
$146k
NIGMS NIH HHS F30 GM116455NIGMS NIH HHS R01 GM120322NIGMS NIH HHS T32 GM007183
6 · The paper itself

Abstract

Adhesion G-protein-coupled receptors (aGPCRs) play critical roles in diverse cellular processes in neurobiology, development, immunity, and numerous diseases. The lack of molecular understanding of their activation mechanisms, especially with regard to the transmembrane domains, hampers further studies to facilitate aGPCR-targeted drug development. Latrophilin-1/ADGRL1 is a model aGPCR that regulates synapse formation and embryogenesis, and its mutations are associated with cancer and attention-deficit/hyperactivity disorder. Here, we established functional assays to monitor latrophilin-1 function and showed the activation of latrophilin-1 by its endogenous agonist peptide. Via a comprehensive mutagenesis screen, we identified transmembrane domain residues essential for latrophilin-1 basal activity and for agonist peptide response. Strikingly, a cancer-associated mutation exhibited increased basal activity and failed to rescue the embryonic developmental phenotype in transgenic worms. These results provide a mechanistic foundation for future aGPCR-targeted drug design.

Indexed as

Membrane ArchitectureMolecular BiologyProtein Structure Aspects

Identifiers

PMID30428326
PMCPMC6137404
OpenAlexW2802667423

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.