SNARE-mediated protein trafficking in macrophages

巨噬细胞中 SNARE 介导的蛋白质运输

• 批准号: nhmrc : 456095
• 负责人: Prof Jennifer Stow
• 金额: $ 52.3万
• 依托单位: The University of Queensland
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2008
• 资助国家: 澳大利亚
• 起止时间: 2008-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/snare-mediated-protein-trafficking-macrophages/100251
• 关键词: SNARE; mediated; protein; trafficking; macrophages

Macrophages are white blood cells that provide front line defence against infection by initiating inflammatory responses by ingesting or phagocytosing microbes and by releasing soluble messengers (cytokines) to recruit other immune cells. These defensive functions require extensive trafficking of proteins within the macrophages. Protein trafficking is orchestrated in part by a family of membrane fusion proteins called SNAREs. By defining the relevant SNAREs, we have recently discovered a much acclaimed and novel pathway that allows efficient, combined cytokine secretion and phagocytosis in macrophages. Our studies proposed here will now expand on this discovery by comparing the phagocytic process, in terms of SNARE-mediated membrane and cytokine trafficking, for a wide range of microbes, highlighting differences that could provide new avenues for drug development. Moreover, since our strategy of using SNAREs to investigate and map trafficking pathways has proven so successful, we will now launch a major large-scale initiative to study ALL SNARE-mediated trafficking pathways in macrophages using a discovery pipeline of assays, including live cell imaging, we have developed. This will provide valuable information on many SNAREs including those associated with disease, and will elucidate trafficking pathways governing all macrophage actions in immunity, including cytokine secretion and antigen presentation. All of these pathways are highly relevant to current drug targets being used clinically or studied in inflammatory disease and for the development of vaccines.

巨噬细胞是白细胞，通过摄入或吞噬微生物并释放可溶性使者（细胞因子）来募集其他免疫细胞来引发炎症反应，从而为防御感染提供前线防御。这些防御功能需要在巨噬细胞中广泛贩运蛋白质。蛋白质运输的部分由称为Snares的膜融合蛋白家族策划。通过定义相关的网罗，我们最近发现了一种广受赞誉和新颖的途径，可以在巨噬细胞中有效，组合的细胞因子分泌和吞噬作用。我们在这里提出的研究将通过比较吞噬细胞介导的膜和细胞因子运输的吞噬过程来扩展这一发现，该过程对广泛的微生物进行了比较，突出了可能为药物开发提供新的途径的差异。此外，由于我们使用网res进行调查和映射贩运途径的策略已被证明是如此成功，因此我们现在将发起一项重大的大规模计划，以使用发现的测定管道来研究巨噬细胞中所有的巨噬细胞贩运途径，包括活细胞成像， ，我们已经发展了。这将提供有关许多网罗（包括与疾病相关的小麻网）的宝贵信息，并将阐明管理所有巨噬细胞行动的贩运途径，包括细胞因子分泌和抗原表现。所有这些途径与当前在临床上使用或在炎症性疾病和疫苗开发中使用的药物靶标高度相关。