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Drosophila?Pkaap regulates Rab4/Rab11-dependent traffic and Rab11 exocytosis of innate immune cargo

机译:果蝇Pkaap调节Rab4 / Rab11依赖的交通和Rab11胞吐的先天免疫货物。

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The secretion of immune-mediators is a critical step in the host innate immune response to pathogen invasion, and Rab GTPases have an important role in the regulation of this process. Rab4/Rab11 recycling endosomes are involved in the sorting of immune-mediators into specialist Rab11 vesicles that can traffic this cargo to the plasma membrane; however, how this sequential delivery process is regulated has yet to be fully defined. Here, we report that?Drosophila?Pkaap, an orthologue of the human dual-specific A-kinase-anchoring protein 2 or D-AKAP2 (also called AKAP10), appeared to have a nucleotide-dependent localisation to Rab4 and Rab11 endosomes. RNAi silencing of?pkaap?altered Rab4/Rab11 recycling endosome morphology, suggesting that Pkaap functions in cargo sorting and delivery in the secretory pathway. The depletion of?pkaap?also had a direct effect on Rab11 vesicle exocytosis and the secretion of the antimicrobial peptide Drosomycin at the plasma membrane. We propose that Pkaap has a dual role in antimicrobial peptide traffic and exocytosis, making it an essential component for the secretion of inflammatory mediators and the defence of the host against pathogens.
机译:免疫介质的分泌是宿主对病原体入侵的先天免疫反应的关键步骤,Rab GTPases在调节此过程中起重要作用。 Rab4 / Rab11回收内体参与将免疫介体分类为专业的Rab11囊泡,该囊泡可将这种货物运输到质膜上。但是,如何对这种顺序交付过程进行监管尚待完全定义。在这里,我们报道果蝇Pkaap,人类双重特异性A激酶锚定蛋白2或D-AKAP2(也称为AKAP10)的直系同源物,似乎对Rab4和Rab11内体具有核苷酸依赖性。 pkaap的RNAi沉默改变了Rab4 / Rab11回收内体的形态,表明Pkaap在货物分类和分泌途径中发挥作用。 “ pkaap”的耗竭也直接影响Rab11囊泡的胞吐作用和抗菌肽果霉素在质膜的分泌。我们建议Pkaap在抗菌肽运输和胞吐作用中具有双重作用,使其成为炎症介质分泌和宿主抵抗病原体的必不可少的成分。

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