The Osiris family genes function as novel regulators of the tube maturation process in the Drosophila trachea.
The Osiris family genes function as novel regulators of the tube maturation process in the Drosophila trachea.
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DOI：
10.1371/journal.pgen.1010571
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发表时间：
2023-01
期刊：
影响因子：
4.5
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中科院分区：
文献类型：
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果蝇气管是研究管形态发生的首要模型。连续管形成后，管成熟随之而来。气管管的成熟始于心尖分泌脉冲，该脉冲沉积细胞外基质成分以形成基于几丁质的心尖腔基质（aECM）。然后，该 aECM 被清除，随后带带皱襞成熟。最后，空气充满管子。同时，维持细胞连接以确保管的完整性。先前的研究已经确定了蛋白质运输途径的几个关键成分（内质网、高尔基体、几种内体），这些成分调节 aECM 的分泌和清除以及细胞连接的维持。 Osiris (Osi) 基因家族位于染色体 3R 83D4-E3 上的三倍致死 (Tpl) 基因座，并表现出剂量敏感性。在这里，我们发现三个 Osi 基因（Osi9、Osi15、Osi19）在管成熟过程中冗余地调节粘附连接 (AJ) 维持、管腔间隙、带带皱襞形成、管形态和空气填充。 Osi 蛋白在内体（含 Rab7 的晚期内体、含 Rab11 的循环内体、含 Lamp 的溶酶体）中的定位以及 Osi 突变体中这些内体的减少表明 Osi 基因通过内体介导的运输在管成熟中可能发挥作用。我们分别分析了合子 rab11 和 rab7 突变体的管成熟，以确定是否需要内体介导的运输。有趣的是，在 rab11 中观察到类似的管成熟缺陷，但在 rab7 突变体中没有观察到，这表明在此过程中涉及 Rab11 介导的运输，而不是 Rab7 介导的运输。为了研究 Osi 基因是否主要通过维持含有 Rab11 的内体来调节管成熟，我们在 Osi 突变体气管中过表达 rab11。令人惊讶的是，没有观察到明显的救援。因此，增加内体数量不足以挽救 Osi 突变体的管成熟缺陷。这些结果表明，Osi 基因调节内体介导的运输的其他方面，或调节在管成熟过程中与 Rab11 介导的运输汇聚或平行起作用的未知机制。果蝇气管是研究管状器官形成的保守和基本机制的理想模型系统。在人类中，管状器官包括但不限于肺、肾和血管。管形成缺陷会导致严重的人类疾病，例如多囊肾病。管子开始形成后，它们将继续成熟到其功能长度和直径，对于气管和肺部来说，将充满空气。蛋白质运输途径涉及将蛋白质运送到最终目的地，在管形成过程的各个步骤中发挥着重要作用。先前的研究已经确定了蛋白质运输途径（内质网、高尔基体、内体）中的几个关键成分，它们在管成熟过程中调节各种过程。我们鉴定了 Osiris 蛋白，它是管成熟所必需的，包括维持细胞连接、清除顶端腔、形成带状褶皱以防止管塌陷和空气填充。此外，Osi 蛋白可能通过内体介导的运输来调节管成熟。这项工作将提高我们对 Osi 基因功能和管成熟过程中囊泡运输的理解。
Drosophila trachea is a premier model to study tube morphogenesis. After the formation of continuous tubes, tube maturation follows. Tracheal tube maturation starts with an apical secretion pulse that deposits extracellular matrix components to form a chitin-based apical luminal matrix (aECM). This aECM is then cleared and followed by the maturation of taenidial folds. Finally, air fills the tubes. Meanwhile, the cellular junctions are maintained to ensure tube integrity. Previous research has identified several key components (ER, Golgi, several endosomes) of protein trafficking pathways that regulate the secretion and clearance of aECM, and the maintenance of cellular junctions. The Osiris (Osi) gene family is located at the Triplo-lethal (Tpl) locus on chromosome 3R 83D4-E3 and exhibits dosage sensitivity. Here, we show that three Osi genes (Osi9, Osi15, Osi19), function redundantly to regulate adherens junction (AJ) maintenance, luminal clearance, taenidial fold formation, tube morphology, and air filling during tube maturation. The localization of Osi proteins in endosomes (Rab7-containing late endosomes, Rab11-containing recycling endosomes, Lamp-containing lysosomes) and the reduction of these endosomes in Osi mutants suggest the possible role of Osi genes in tube maturation through endosome-mediated trafficking. We analyzed tube maturation in zygotic rab11 and rab7 mutants, respectively, to determine whether endosome-mediated trafficking is required. Interestingly, similar tube maturation defects were observed in rab11 but not in rab7 mutants, suggesting the involvement of Rab11-mediated trafficking, but not Rab7-mediated trafficking, in this process. To investigate whether Osi genes regulate tube maturation primarily through the maintenance of Rab11-containing endosomes, we overexpressed rab11 in Osi mutant trachea. Surprisingly, no obvious rescue was observed. Thus, increasing endosome numbers is not sufficient to rescue tube maturation defects in Osi mutants. These results suggest that Osi genes regulate other aspects of endosome-mediated trafficking, or regulate an unknown mechanism that converges or acts in parallel with Rab11-mediated trafficking during tube maturation. The Drosophila trachea is the ideal model system to study conserved and fundamental mechanisms of tubular organ formation. In humans, tubular organs include, but are not limited to, the lungs, kidneys, and blood vessels. Defects in tube formation cause severe human diseases, such as polycystic kidney disease. After tubes begin to form, they will continue to mature to their functional lengths and diameters, and in the case of tracheae and lungs, will fill with air. The protein trafficking pathway, which is involved in delivering proteins to their final destinations, is heavily involved in various steps of the tube formation process. Previous studies have identified several key components within the protein trafficking pathway (ER, Golgi, endosomes) that regulate various processes during tube maturation. We identified the Osiris proteins, which are required for tube maturation including the maintenance of cellular junctions, clearance of the apical lumen, formation of taenidial folds to prevent the collapse of the tube, and air filling. In addition, Osi proteins regulate tube maturation potentially through endosome-mediated trafficking. This work will improve our understanding of the function of Osi genes and vesicular trafficking in the tube maturation process.
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