Evidence map›Paper›PMID 41124273›Full record

ArticleScience advances2025

The chloride intracellular channel 1 (CLIC1) is essential for microglial morphodynamics and neuroinflammation.

Ali Rifat, Tom Bickel, Patricia Kreis, Thorsten Trimbuch, Julia Onken, Andranik Ivanov, Giulia Albertini, Dieter Beule, Michele Mazzanti, Harpreet Singh and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–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

2 citing papers in PubMed.

  1. Article
  2. 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

14 authors.

Ali RifatInstitute of Neurophysiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany.ORCID 0000-0001-5801-4358
Tom BickelInstitute of Neurophysiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Patricia KreisInstitute of Biochemistry and Molecular Biology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany.ORCID 0000-0002-1702-4805
Thorsten TrimbuchInstitute of Neurophysiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany.ORCID 0000-0001-7512-8955
Julia OnkenDepartment of Neurosurgery, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Andranik IvanovCore Unit Bioinformatics, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.ORCID 0000-0002-4824-1925
Giulia AlbertiniCentre for Brain and Disease Research, Flanders Institute for Biotechnology (VIB), Leuven, Belgium.ORCID 0000-0002-8215-2432
Dieter BeuleCore Unit Bioinformatics, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.ORCID 0000-0002-3284-0632
Michele MazzantiLaboratory of Cellular and Molecular Physiology, Department of Biosciences, University of Milan, Via Celoria 26, I-20133 Milano, Italy.ORCID 0000-0002-1819-3811
Harpreet SinghDepartment of Physiology and Cell Biology, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.ORCID 0000-0002-6135-1897
Britta J EickholtInstitute of Biochemistry and Molecular Biology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany.ORCID 0000-0001-7873-8687
Bart De StrooperCentre for Brain and Disease Research, Flanders Institute for Biotechnology (VIB), Leuven, Belgium.ORCID 0000-0001-5455-5819
Jörg R P GeigerInstitute of Neurophysiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany.ORCID 0000-0001-9552-4322
Christian MadryInstitute of Neurophysiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany.ORCID 0000-0002-0522-7197

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Microglial functions rely on their morphodynamic versatility and inflammatory response, yet the molecular determinants, particularly ion channels and receptors, remain poorly understood. Here, we identify chloride intracellular channel 1 (CLIC1), a protein known to exist in both soluble and membrane-associated forms, as highly enriched in human and murine microglia, with minimal expression in other brain cells. Acute blockade or genetic deletion of CLIC1 markedly attenuates microglial surveillance by reducing ramification and motility, without affecting chemotaxis. This phenotype is recapitulated in xenografted human microglia and human brain tissue. Mechanistically, CLIC1 effects involve interactions with actin-binding ezrin, radixin, and moesin (ERM) proteins, suggesting a role in linking the plasma membrane to the cytoskeleton. Contrary to its name, CLIC1 functions are chloride-independent and thus unlikely to reflect ion channel activity. This is supported by patch-clamp electrophysiology revealing lack of chloride conductance in surveillant microglia. Following ATP-evoked activation, CLIC1 blockade strongly suppresses NLRP3-dependent interleukin-1β release, suggesting therapeutic potential against neuroinflammation.

Indexed as

Chloride ChannelsMicrogliaNeuroinflammatory DiseasesAnimalsChloridesCytoskeletal ProteinsEzrinHumansInflammationInterleukin-1betaMembrane ProteinsMiceMice, KnockoutMicrofilament ProteinsNLR Family, Pyrin Domain-Containing 3 ProteinChloride ChannelsChloridesCLIC1 protein, humanClic1 protein, mouseCytoskeletal ProteinsEzrinInterleukin-1betaMembrane ProteinsMicrofilament ProteinsmoesinNLR Family, Pyrin Domain-Containing 3 Proteinradixin

Identifiers

PMID41124273
PMCPMC12542960

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.