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

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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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Funding Information
  • Agence Nationale de la Recherche (ANR-22-CE13-0037-01)
  • Agence Nationale de la Recherche (ANR-10-INBS-0004-01)
  • Agence Nationale de la Recherche (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)
  • National Institutes of Health (NIH R21OD033663)

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