Evidence map›Paper›PMID 33171122›Full record

ArticleMolecular cell2020

LRRC8A:C/E Heteromeric Channels Are Ubiquitous Transporters of cGAMP.

Lauren J Lahey, Rachel E Mardjuki, Xianlan Wen, Gaelen T Hess, Christopher Ritchie, Jacqueline A Carozza, Volker Böhnert, Merritt Maduke, Michael C Bassik, Lingyin Li

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed
8.1field-weighted citation impact, top 2% 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

112 citing papers in PubMed, 180 citations in OpenAlex.

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52 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

10 authors at 1 institution in 1 country.

Lauren J LaheyBiophysics Program, Stanford University, Stanford, CA 94305, USA; Stanford ChEM-H, Stanford University, Stanford, CA 94305, USA.
Rachel E MardjukiStanford ChEM-H, Stanford University, Stanford, CA 94305, USA; Department of Chemistry, Stanford University, Stanford, CA 94305, USA.
Xianlan WenDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA.
Gaelen T HessStanford ChEM-H, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Christopher RitchieStanford ChEM-H, Stanford University, Stanford, CA 94305, USA; Department of Biochemistry, Stanford University, Stanford, CA 94305, USA.
Jacqueline A CarozzaStanford ChEM-H, Stanford University, Stanford, CA 94305, USA; Department of Chemistry, Stanford University, Stanford, CA 94305, USA.
Volker BöhnertStanford ChEM-H, Stanford University, Stanford, CA 94305, USA; Department of Biochemistry, Stanford University, Stanford, CA 94305, USA.
Merritt MadukeDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA.
Michael C BassikStanford ChEM-H, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Lingyin LiStanford ChEM-H, Stanford University, Stanford, CA 94305, USA; Department of Biochemistry, Stanford University, Stanford, CA 94305, USA. Electronic address: lingyinl@stanford.edu.
Stanford University · US

Funding

Accelerating drug development and repurposing using systematic genetic interactioDP2HD084069 · NICHD · STANFORD UNIVERSITY · PI BASSIK, MICHAEL C · 2014 to 2014
$2.4M
Chemical biology of innate immunity for treating cancer and autoimmunityDP2CA228044 · NCI · STANFORD UNIVERSITY · PI LI, LINGYIN · 2017 to 2017
$2.4M
Stanford Chem-H Chemistry/Biology Interface Predoctoral Training ProgramT32GM120007 · NIGMS · STANFORD UNIVERSITY · PI BERTOZZI, CAROLYN · 2016 to 2020
$1.2M
NCI NIH HHS DP2 CA228044NICHD NIH HHS DP2 HD084069NIGMS NIH HHS T32 GM120007
6 · The paper itself

Abstract

Extracellular 2'3'-cyclic-GMP-AMP (cGAMP) is an immunotransmitter exported by diseased cells and imported into host cells to activate the innate immune STING pathway. We previously identified SLC19A1 as a cGAMP importer, but its use across human cell lines is limited. Here, we identify LRRC8A heteromeric channels, better known as volume-regulated anion channels (VRAC), as widely expressed cGAMP transporters. LRRC8A forms complexes with LRRC8C and/or LRRC8E, depending on their expression levels, to transport cGAMP and other 2'3'-cyclic dinucleotides. In contrast, LRRC8D inhibits cGAMP transport. We demonstrate that cGAMP is effluxed or influxed via LRRC8 channels, as dictated by the cGAMP electrochemical gradient. Activation of LRRC8A channels, which can occur under diverse stresses, strongly potentiates cGAMP transport. We identify activator sphingosine 1-phosphate and inhibitor DCPIB as chemical tools to manipulate channel-mediated cGAMP transport. Finally, LRRC8A channels are key cGAMP transporters in resting primary human vasculature cells and universal human cGAMP transporters when activated.

Indexed as

CRISPR-Cas SystemsBiological TransportCyclopentanesHumansIndansLysophospholipidsMembrane ProteinsNucleotides, CyclicSphingosineSTING ProteinU937 Cells4-(2-butyl-6,7-dichlor-2-cyclopentyl-indan-1-one-5-yl)oxybutyric acidcyclic guanosine monophosphate-adenosine monophosphateCyclopentanesIndansLRRC8A protein, humanLysophospholipidsMembrane ProteinsNucleotides, CyclicSphingosinesphingosine 1-phosphateSTING1 protein, humanSTING Protein2’3’-cGAMPcGAMPcyclic dinucleotideLRRC8ALRRC8CLRRC8DSTINGtransportervasculatureVRAC

Identifiers

PMID33171122
PMCPMC12629894
OpenAlexW3104130940

What OpenQuestion holds

Textmetadata
LicenceTDM
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.