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A defining member of the new cysteine-cradle family is a transient aECM protein involved in signalling skin damage
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The apical extracellular matrix acts as crucial barrier, and communicates with the epidermis to trigger protective responses following injury or infection. In C. elegans , we previously showed that mutants lacking cuticle furrows exhibit persistent immune activation (PIA). In a genetic suppressor screen, we identified spia-1 as a key gene downstream of furrow collagens and upstream of immune signaling. spia-1 expression oscillates during larval development, peaking between each moult together with precuticle and cuticule components. It encodes a secreted precuticular protein that transiently localizes to furrows. It shares a novel cysteine-cradle domain (CCD-aECM) with other aECM proteins, predicted to bind proteins with an exposed hydrophobic α helix. SPIA - 1 is proposed to act as a sensor of cuticle damage, mediating immune activation in response to furrow loss and might be part of a checkpoint during the establishment of the new cuticle. This research reinforces the notion of an intricate interplay between cuticle integrity and epidermal immune activation in C. elegans .
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