Sonntag Thomas, Omi Shizue, Andreeva Antonina, Eichelbrenner Jeanne, Chisholm Andrew D, Ward Jordan D, Pujol Nathalie
Aix Marseille Univ, INSERM, CNRS, CIML, Turing Centre for Living Systems, Marseille, France.
European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
bioRxiv. 2024 Nov 5:2024.04.11.589058. doi: 10.1101/2024.04.11.589058.
Apical extracellular matrices (aECMs) act as crucial barriers, and communicate with the epidermis to trigger protective responses following injury or infection. In , 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). In a genetic suppressor screen, we identified as a key gene downstream of furrow collagens and upstream of immune signalling. 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. SPIA1 mediates immune activation in response to furrow loss and is proposed to act as a sensor of cuticle damage. This research provides a molecular insight into intricate interplay between cuticle integrity and epidermal immune activation in .
顶端细胞外基质（aECMs）起着关键屏障的作用，并与表皮进行沟通，以在损伤或感染后触发保护性反应。在[具体情境未提及]中，皮肤的aECM，即角质层，由表皮产生，并饰有周期性的圆周沟。我们之前表明，缺乏角质层沟的突变体表现出持续免疫激活（PIA）。在一项遗传抑制因子筛选中，我们鉴定出[具体基因未提及]作为沟胶原蛋白下游和免疫信号上游的关键基因。[具体基因未提及]的表达在幼虫发育过程中振荡，在每次蜕皮之间达到峰值，同时与形成角质层成分的过程同步。它编码一种定位于沟的分泌蛋白。SPIA-1与其他aECM蛋白共享一个新的半胱氨酸摇篮结构域。SPIA1介导对沟缺失的免疫激活，并被认为是角质层损伤的传感器。这项研究为[具体情境未提及]中角质层完整性与表皮免疫激活之间的复杂相互作用提供了分子层面的见解。
