Lysosomes degrade macromolecular cargos, recycle catabolites, and serve as signaling platforms to maintain cell homeostasis, but their role at the tissue level is unclear. Here, we investigate lysosome regulation and function during C. elegans molting, a specialized extracellular matrix (ECM) remodeling process essential for larval development. We found that lysosomes are specifically activated in the epidermis at molt when the apical ECM (cuticle) is being replaced. Impaired lysosome function affects endocytic cargo degradation, suppresses elevated protein synthesis at molt, and causes molting defects. Disturbance of ECM-epidermis attachments triggers lysosomal activation and induces expression of the vacuolar H+-ATPase (V-ATPase), which is mediated by the GATA transcription factor ELT-3 and the STAT family protein STA-2. Our study reveals an ECM-to-nucleus signaling pathway that activates lysosomes to facilitate ECM remodeling essential for larval development.

中文翻译：

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ECM到核的信号通路激活线虫的线虫幼虫发育。

溶酶体降解大分子货物，回收分解代谢产物，并充当维持细胞稳态的信号传递平台，但它们在组织水平上的作用尚不清楚。在这里，我们调查线虫蜕皮过程中的溶酶体调控和功能，这是幼虫发育必不可少的专门的细胞外基质（ECM）重塑过程。我们发现，当替换顶部的ECM（表皮）时，溶酶体在蜕皮的表皮中被特异性激活。溶酶体功能受损会影响内吞货物降解，抑制蜕皮中蛋白质合成的升高，并导致蜕皮缺陷。ECM表皮附着的干扰触发溶酶体激活并诱导液泡H + -ATPase（V-ATPase）的表达，该表达由GATA转录因子ELT-3和STAT家族蛋白STA-2介导。