A defining member of the new cysteine-cradle family is an aECM protein signalling skin damage in C. elegans
Year: 2025
Type: article
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.
Source: PLoS Genetics
Institutions: Centre National de la Recherche Scientifique, Inserm, Aix-Marseille Université, Centre d’Immunologie de Marseille-Luminy, European Bioinformatics Institute, Dynamique et Nanoenvironnement des Membranes Biologiques, University of California San Diego, University of California, Santa Cruz
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
Funders: National Science Foundation, Biogen, Aix-Marseille Université, Infrastructures en Biologie Santé et Agronomie, Agence Nationale de la Recherche, Centre National de la Recherche Scientifique, National Institutes of Health, Directorate for Biological Sciences, Biotechnology and Biological Sciences Research Council, National Institute of General Medical Sciences
Awards: G1190173965, CenTuri : Centre Turing des Systèmes vivants, INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE, G2111793168, How does the skin sense damage?, G2441619162, G262592543, UKRI/BBSRC-NSF/BIO: Unifying Pfam protein sequence and ECOD structural classifications with structure models, G381665449, G4238244635, G461943475, G4950536974, G5076921152, Illuminating apical extracellular matrix structure and biogenesis, G5553438487, G7011901419, G7240651115, G7913377617, France-BioImaging (Biological Imaging Next-Generation Instrument), Développment d'une infrastructure française distribuée coordonnée, G9000028377, G9000274861, Caenorhabditis Genetics Center
OpenAlex ID: W4404168084