PDF(Pubmed)
Abstract：
Intracellular organelles support cellular physiology in diverse conditions. In the skin, epidermal keratinocytes undergo differentiation with gradual changes in cellular physiology, accompanying remodeling of lysosomes and the Golgi apparatus. However, it was not known whether changes in Golgi and lysosome morphology and their redistribution were linked. Here, we show that disassembled Golgi is distributed in close physical apposition to lysosomes in differentiated keratinocytes. This atypical localization requires the Golgi tethering protein GRASP65, which is associated with both the Golgi and lysosome membranes. Depletion of GRASP65 results in the loss of Golgi-lysosome apposition and the malformation of lysosomes, defined by their aberrant morphology, size, and function. Surprisingly, a trans-Golgi enzyme and secretory Golgi cargoes are extensively localized to the lysosome lumen and secreted to the cell surface, contributing to total protein secretion of differentiated keratinocytes but not in proliferative precursors, indicating that lysosomes acquire specialization during differentiation. We further demonstrate that the secretory function of the Golgi apparatus is critical to maintain keratinocyte lysosomes. Our study uncovers a novel form of Golgi-lysosome cross-talk and its role in maintaining specialized secretory lysosomes in differentiated keratinocytes.
摘要：
细胞内细胞器支持不同条件下的细胞生理学。在皮肤上，表皮角质形成细胞随着细胞生理学的逐渐变化而分化，伴随着溶酶体和高尔基体的重塑。然而,目前尚不清楚高尔基体和溶酶体形态的变化及其再分布是否相关.这里,我们表明，在分化的角质形成细胞中，分裂的高尔基体与溶酶体紧密物理并置。这种非典型的定位需要高尔基体束缚蛋白GRASP65，它与高尔基体和溶酶体膜都相关。GRASP65的耗尽导致高尔基体-溶酶体并置的丧失和溶酶体的畸形,由它们的异常形态定义，尺寸,和功能。令人惊讶的是,一种反式高尔基体酶和分泌型高尔基体被广泛地定位在溶酶体内腔并分泌到细胞表面,促进分化的角质形成细胞的总蛋白质分泌，但不促进增殖前体，表明溶酶体在分化过程中获得专业化。我们进一步证明高尔基体的分泌功能对于维持角质形成细胞溶酶体至关重要。我们的研究揭示了高尔基体溶酶体串扰的一种新形式及其在维持分化的角质形成细胞中的专门分泌溶酶体中的作用。
