Evidence map›Paper›PMID 39461969›Full record

ArticleScientific reports2024

The Tmem16a chloride channel is required for mucin maturation after secretion from goblet-like cells in the Xenopus tropicalis tadpole skin.

Eamon Dubaissi, Emma N Hilton, Sarah Lilley, Richard Collins, Charlotte Holt, Peter March, Henry Danahay, Martin Gosling, Richard K Grencis, Ian S Roberts and 1 more

Abstract read
In one paragraph

Article in Scientific reports, 2024. 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. Article
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

11 authors.

Eamon Dubaissi *School of Biological Sciences, University of Manchester, Manchester, M13 9PT, UK.
Emma N Hilton *School of Biological Sciences, University of Manchester, Manchester, M13 9PT, UK.
Sarah LilleySussex Drug Discovery Centre, University of Sussex, Falmer, Brighton, BN1 9QJ, UK.
Richard CollinsSchool of Biological Sciences, University of Manchester, Manchester, M13 9PT, UK.
Charlotte HoltSchool of Biological Sciences, University of Manchester, Manchester, M13 9PT, UK.
Peter MarchSchool of Biological Sciences, University of Manchester, Manchester, M13 9PT, UK.
Henry DanahayEnterprise Therapeutics, Sussex Innovation Centre, Science Park Square, Falmer, Brighton, BN1 9SB, UK.
Martin GoslingSussex Drug Discovery Centre, University of Sussex, Falmer, Brighton, BN1 9QJ, UK.
Richard K GrencisSchool of Biological Sciences, University of Manchester, Manchester, M13 9PT, UK.
Ian S RobertsSchool of Biological Sciences, University of Manchester, Manchester, M13 9PT, UK.
David J ThorntonSchool of Biological Sciences, University of Manchester, Manchester, M13 9PT, UK. dave.thornton@manchester.ac.uk.ORCID 0000-0001-7148-1970

Funding

Biotechnology and Biological Sciences Research Council BB/W006456/1Biotechnology and Biological Sciences Research Council IAA 403National Centre for the Replacement, Refinement and Reduction of Animals in Research NC/S001034/1
6 · The paper itself

Abstract

The TMEM16A chloride channel is proposed as a therapeutic target in cystic fibrosis, where activation of this ion channel might restore airway surface hydration and mitigate respiratory symptoms. While TMEM16A is associated with increased mucin production under stimulated or pro-inflammatory conditions, its role in baseline mucin production, secretion and/or maturation is less well understood. Here, we use the Xenopus tadpole skin mucociliary surface as a model of human upper airway epithelium to study Tmem16a function in mucus production. We found that Xenopus tropicalis Tmem16a is present at the apical membrane surface of tadpole skin small secretory cells that express canonical markers of mammalian "goblet cells" such as Foxa1 and spdef. X. tropicalis Tmem16a functions as a voltage-gated, calcium-activated chloride channel when transfected into mammalian cells in culture. Depletion of Tmem16a from the tadpole skin results in dysregulated mucin maturation post-secretion, with secreted mucins having a disrupted molecular size distribution and altered morphology assessed by sucrose gradient centrifugation and electron microscopy, respectively. Our results show that in the Xenopus tadpole skin, Tmem16a is necessary for normal mucus barrier formation and demonstrate the utility of this model system to discover new biology relevant to human mucosal biology in health and disease.

Indexed as

Anoctamin-1Goblet CellsLarvaMucinsSkinXenopusAnimalsChloride ChannelsHumansXenopus ProteinsAnoctamin-1Chloride ChannelsMucinsXenopus ProteinsIon channelMucinMucusTMEM16AXenopus tropicalis

Identifiers

PMID39461969
PMCPMC11514049

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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.