Evidence map›Paper›PMID 35833483›Full record

ArticleJournal of cell science2022

A Zn2+-triggered two-step mechanism of CLIC1 membrane insertion and activation into chloride channels.

Lorena Varela, Alex C Hendry, Joseph Cassar, Ruben Martin-Escolano, Diego Cantoni, Felipe Ossa, John C Edwards, Vahitha Abdul-Salam, Jose L Ortega-Roldan

Open access · hybridAbstract read
In one paragraph

Article in Journal of cell science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.7field-weighted citation impact, top 33% 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

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. CLIC1 Supports Mechanisms Related to Platelet Activation and Thrombosis.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2025
    Article
  3. Intracellular Chloride Channels: A Rising Target in Lung Disease Research.Journal of respiratory biology and translational medicine · 2025
    Article
  4. Review
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

9 authors at 4 institutions in 2 countries.

Lorena VarelaSchool of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.ORCID 0000-0002-0743-9441
Alex C HendrySchool of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.
Joseph CassarSchool of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.
Ruben Martin-EscolanoSchool of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.
Diego CantoniMedway School of Pharmacy, The Universities of Kent and Greenwich at Medway, Chatham ME7 4TB, UK.
Felipe OssaCentre for Cardiovascular Medicine and Device Innovation, William Harvey Research Institute (WHRI), Faculty of Medicine and Dentistry, Queen Mary University of London, Room 213, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
John C EdwardsDepartment of Internal Medicine, St Louis University, 3635 Vista Ave., St Louis, MO 63110, USA.
Vahitha Abdul-SalamCentre for Cardiovascular Medicine and Device Innovation, William Harvey Research Institute (WHRI), Faculty of Medicine and Dentistry, Queen Mary University of London, Room 213, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
Jose L Ortega-RoldanSchool of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.ORCID 0000-0002-6316-4390
University of Kent · GBQueen Mary University of London · GBMedway School of Pharmacy · GBSaint Louis University · US

Funding

Alfonso Martin Escudero FoundationBarts CharityUniversity of KentWellcome TrustWellcome Trust 207743/Z/17/Z
6 · The paper itself

Abstract

The chloride intracellular channel (CLIC) protein family displays the unique feature of altering its structure from a soluble form to a membrane-bound chloride channel. CLIC1, a member of this family, is found in the cytoplasm or in internal and plasma membranes, with membrane relocalisation linked to endothelial disfunction, tumour proliferation and metastasis. The molecular switch promoting CLIC1 activation remains under investigation. Here, cellular Cl- efflux assays and immunofluorescence microscopy studies have identified intracellular Zn2+ release as the trigger for CLIC1 activation and membrane insertion. Biophysical assays confirmed specific binding to Zn2+, inducing membrane association and enhancing Cl- efflux in a pH-dependent manner. Together, our results identify a two-step mechanism with Zn2+ binding as the molecular switch promoting CLIC1 membrane insertion, followed by pH-mediated activation of Cl- efflux.

Indexed as

Chloride ChannelsChloridesBiological TransportCell MembraneZincChloride ChannelsChloridesZincBiophysicsChannel activationChloride channelLipid–protein interactionMembrane protein

Identifiers

PMID35833483
PMCPMC9511705
OpenAlexW4285388663

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.