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Cited by 9Invertebrate Immune Response MechanismsGenetics, Aging, and Longevity in Model OrganismsNeurobiology and Insect Physiology Research

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A defining member of the new cysteine-cradle family is an aECM protein signalling skin damage in C. elegans

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Sonntag, Thomas, Omi, Shizue, Andreeva, Antonina, Valotteau, Claire, Eichelbrenner, Jeanne, Chisholm, Andrew D., Ward, Jordan D., Pujol, Nathalie·2025·PLOS Genetics
DOI 10.1371/journal.pgen.1011593PMC PMC11925461

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Abstract

Apical extracellular matrices (aECMs) act as crucial barriers, and communicate with the epidermis to trigger protective responses following injury or infection. In Caenorhabditis elegans , the skin aECM, the cuticle, is produced by the epidermis and is decorated with periodic circumferential furrows. We previously showed that mutants lacking cuticle furrows exhibit persistent immune activation (PIA), providing a valuable model to study the link between cuticle damage and immune response. In a genetic suppressor screen, we identified spia-1 as a key gene downstream of furrow collagens and upstream of immune signalling. spia-1 expression oscillates during larval development, peaking between each moult together with patterning cuticular components. It encodes a secreted protein that localises to furrows. SPIA-1 shares a novel cysteine-cradle domain with other aECM proteins. SPIA - 1 mediates immune activation in response to furrow loss and is proposed to act as an extracellular signal activator of cuticle damage. This research provides a molecular insight into intricate interplay between cuticle integrity and epidermal immune activation in C. elegans .

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Metadata

Authors
Sonntag, T., Omi, S., Andreeva, A., Valotteau, C., Eichelbrenner, J., Chisholm, A. D., Ward, J. D., & Pujol, N.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • European Bioinformatics Institute (GB)
  • Inserm (FR)
  • University of California, Santa Cruz (US)
Corresponding author
Pujol, Nathalie
ORCID
Venue
PLOS Genetics
Publisher
Public Library of Science (PLoS)
Published
2025-03-20
Volume
21
Issue
3
Pages
e1011593
ISSN
  • 1553-7390 (ISSN-L)
  • 1553-7404
DOI
10.1371/journal.pgen.1011593
PMC
PMC11925461
OpenAlex
W4404168084
Cited by
9
References
3
Citations by year
2026: 8 · 2025: 1
FWCI
3.31
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Genetics (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by-nc-nd)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
  • HAL (submittedVersion)
  • HAL AMU (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Agence Nationale de la Recherche (ANR-22-CE13-0037-01, ANR-10-INBS-0004-01, ANR-16-CONV-0001)
  • Aix-Marseille Université (Excellence Initiative of Aix-Marseille University - A*MIDEX)
  • ATIP Avenir
  • Itmo cancer (Aviesan on funds Cancer 2021)
  • CNRS
  • Aix Marseille University
  • Biotechnology and Biological Sciences Research Council (BB/X012492/1)
  • National Institutes of Health (NIH R35GM134970, NIH R21OD033663)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Invertebrate Immune Response Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
Keywords
apical extracellular matrix, cuticle, extracellular signalling, immune activation, skin damage, Caenorhabditis elegans, molting

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