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

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....

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Main Authors: Thomas Sonntag, Shizue Omi, Antonina Andreeva, Claire Valotteau, Jeanne Eichelbrenner, Andrew D Chisholm, Jordan D Ward, Nathalie Pujol
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-03-01
Series:PLoS Genetics
Online Access:https://doi.org/10.1371/journal.pgen.1011593
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author Thomas Sonntag
Shizue Omi
Antonina Andreeva
Claire Valotteau
Jeanne Eichelbrenner
Andrew D Chisholm
Jordan D Ward
Nathalie Pujol
author_facet Thomas Sonntag
Shizue Omi
Antonina Andreeva
Claire Valotteau
Jeanne Eichelbrenner
Andrew D Chisholm
Jordan D Ward
Nathalie Pujol
author_sort Thomas Sonntag
collection DOAJ
description 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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spelling doaj-art-25c513c9db2d4f36abcfe16d53367ab52025-08-20T03:13:12ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042025-03-01213e101159310.1371/journal.pgen.1011593A defining member of the new cysteine-cradle family is an aECM protein signalling skin damage in C. elegans.Thomas SonntagShizue OmiAntonina AndreevaClaire ValotteauJeanne EichelbrennerAndrew D ChisholmJordan D WardNathalie PujolApical 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.https://doi.org/10.1371/journal.pgen.1011593
spellingShingle Thomas Sonntag
Shizue Omi
Antonina Andreeva
Claire Valotteau
Jeanne Eichelbrenner
Andrew D Chisholm
Jordan D Ward
Nathalie Pujol
A defining member of the new cysteine-cradle family is an aECM protein signalling skin damage in C. elegans.
PLoS Genetics
title A defining member of the new cysteine-cradle family is an aECM protein signalling skin damage in C. elegans.
title_full A defining member of the new cysteine-cradle family is an aECM protein signalling skin damage in C. elegans.
title_fullStr A defining member of the new cysteine-cradle family is an aECM protein signalling skin damage in C. elegans.
title_full_unstemmed A defining member of the new cysteine-cradle family is an aECM protein signalling skin damage in C. elegans.
title_short A defining member of the new cysteine-cradle family is an aECM protein signalling skin damage in C. elegans.
title_sort defining member of the new cysteine cradle family is an aecm protein signalling skin damage in c elegans
url https://doi.org/10.1371/journal.pgen.1011593
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