Evidence map›Paper›PMID 25781344›Full record

ArticleeLife2015

Secreted CLCA1 modulates TMEM16A to activate Ca(2+)-dependent chloride currents in human cells.

Monica Sala-Rabanal, Zeynep Yurtsever, Colin G Nichols, Tom J Brett

Open access · goldAbstract read
In one paragraph

Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
5.3field-weighted citation impact, top 4% 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

67 citing papers in PubMed, 100 citations in OpenAlex.

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  14. Chronic sodium bromide treatment relieves autistic-like behavioral deficits in three mouse models of autism.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022
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  15. A Single-Cell Atlas of Large and Small Airways at Birth in a Porcine Model of Cystic Fibrosis.American journal of respiratory cell and molecular biology · 2022
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  16. CaInternational journal of molecular sciences · 2022
    Article
  17. Polymodal Control of TMEM16x Channels and Scramblases.International journal of molecular sciences · 2022
    Review
  18. Article
  19. Article
  20. Review

7 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

4 authors at 1 institution in 1 country.

Monica Sala-RabanalDepartment of Cell Biology and Physiology, Washington University School of Medicine, St Louis, United States.
Zeynep YurtseverCenter for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, St Louis, United States.
Colin G NicholsDepartment of Cell Biology and Physiology, Washington University School of Medicine, St Louis, United States.
Tom J BrettDepartment of Cell Biology and Physiology, Washington University School of Medicine, St Louis, United States.
Washington University in St. Louis · US

Funding

Rectification &Block of Ion Channel CurrentsR01HL054171 · NHLBI · WASHINGTON UNIVERSITY · PI NICHOLS, COLIN G · 1995 to 2017
$4.5M
STRUCTURAL REGULATION OF CLCA1 ACTIVITYR01HL119813 · NHLBI · WASHINGTON UNIVERSITY · PI BRETT, THOMAS JOHN · 2013 to 2017
$1.9M
NHLBI NIH HHS R01 HL054171NHLBI NIH HHS R01 HL119813
6 · The paper itself

Abstract

Calcium-activated chloride channel regulator 1 (CLCA1) activates calcium-dependent chloride currents; neither the target, nor mechanism, is known. We demonstrate that secreted CLCA1 activates calcium-dependent chloride currents in HEK293T cells in a paracrine fashion, and endogenous TMEM16A/Anoctamin1 conducts the currents. Exposure to exogenous CLCA1 increases cell surface levels of TMEM16A and cellular binding experiments indicate CLCA1 engages TMEM16A on the surface of these cells. Altogether, our data suggest that CLCA1 stabilizes TMEM16A on the cell surface, thus increasing surface expression, which results in increased calcium-dependent chloride currents. Our results identify the first Cl(-) channel target of the CLCA family of proteins and establish CLCA1 as the first secreted direct modifier of TMEM16A activity, delineating a unique mechanism to increase currents. These results suggest cooperative roles for CLCA and TMEM16 proteins in influencing the physiology of multiple tissues, and the pathology of multiple diseases, including asthma, COPD, cystic fibrosis, and certain cancers.

Indexed as

Ion Channel GatingAnoctamin-1Blotting, WesternCalciumCell MembraneChloride ChannelsChloridesHEK293 CellsHumansMembrane PotentialsMicroscopy, ConfocalNeoplasm ProteinsParacrine CommunicationPatch-Clamp TechniquesProtein BindingRNA InterferenceANO1 protein, humanAnoctamin-1CalciumChloride ChannelsChloridesCLCA1 protein, humanNeoplasm Proteinsbiophysicscalcium activated chloride channelscell biologychronic inflammatory airway diseasehumanion channel regulationstructural biology

Identifiers

PMID25781344
PMCPMC4360653
OpenAlexW2147269541

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.