Protein networks involved in biogenesis of the Salmonella proliferative niche

参与沙门氏菌增殖生态位生物发生的蛋白质网络

• 批准号: 261251403
• 负责人: Professor Dr. Ivan Dikic
• 金额: --
• 依托单位: Institut für Biophysik
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/261251403?language=en
• 关键词: Protein; networks; involved; biogenesis; Salmonella

The gram-negative bacterium Salmonella enterica has provided many insights into the infection process of epithelial cells and how intracellular pathogens can manipulate the host endo-membrane system and evade internal defence strategies. We are interested to molecularly characterise membrane dynamics during Salmonella infection, in particular how Salmonella manipulate and recruit membrane sources required for the maintenance and growth of Salmonella containing vacuoles (SCVs). Under non-infected conditions, these pathways are regulated by small Rab GTPases, their effector proteins and membrane fusion machineries such as the homeotypic protein sorting (HOPS) complex. By using mass spectrometry, we have identified the adaptor protein Plekhm1 (Pleckstrin homology domain containing family member 1) as an effector of active Rab7 (Rab7.GTP) that also binds to the HOPS complex. In this proposal we will test whether key Salmonella effector proteins function as regulators of the Salmonella containing membrane compartments and how they may manipulate the endosomal network. Moreover, we will focus on cellular host proteins that interact with bacterial effector proteins and other elements of the lysosomal membrane fusion machinery that may regulate this process through direct interaction or by the modification of the composition of the lysosomal membrane itself. Overall, this proposal addresses key questions on which pathogen- and host-derived compounds contribute to biogenesis of Salmonella containing compartments.

革兰氏阴性细菌肠沙门氏菌为上皮细胞的感染过程以及细胞内病原体如何操纵宿主内膜系统并逃避内部防御策略提供了许多见解。我们感兴趣的是沙门氏菌感染过程中膜动力学的分子特征，特别是沙门氏菌如何操纵和招募含有沙门氏菌的空泡（SCV）的维持和生长所需的膜源。在非感染条件下，这些途径受到小 Rab GTP 酶、其效应蛋白和膜融合机制（如同型蛋白分选 (HOPS) 复合物）的调节。通过使用质谱分析，我们鉴定出接头蛋白 Plekhm1（包含家族成员 1 的 Pleckstrin 同源结构域）是活性 Rab7 (Rab7.GTP) 的效应子，也与 HOPS 复合物结合。在本提案中，我们将测试关键的沙门氏菌效应蛋白是否作为含有膜区室的沙门氏菌的调节剂发挥作用，以及它们如何操纵内体网络。此外，我们将重点关注与细菌效应蛋白和溶酶体膜融合机制的其他元件相互作用的细胞宿主蛋白，这些元件可以通过直接相互作用或通过改变溶酶体膜本身的组成来调节这一过程。总体而言，该提案解决了哪些病原体和宿主衍生的化合物有助于含有沙门氏菌的隔室的生物发生的关键问题。