Regulation of membrane fusion in macrophage phagocytosis

描述（由申请方提供）：吞噬作用对于清除入侵的病原体、外来颗粒和死细胞体至关重要。这一过程的损害导致疾病的发展，包括传染病。令人惊讶的是，尽管该途径的重要性，但关于控制吞噬体成熟的机制的信息有限。特别是，控制内吞区室与吞噬体融合的SNARE复合物的身份是不完整的。我们最近发现SNARE蛋白SNAP 29在巨噬细胞杀死大肠杆菌中起早期作用。基于这一发现，我们提出了SNAP 29与早期内吞SNARE形成融合复合物以控制吞噬体成熟的早期步骤的假设。使用一种独特的多学科方法，我们将确定和表征SNAP 29参与E。大肠杆菌吞噬作用。同时，我们将确定哪些早期内吞SNARE在E.大肠杆菌的吞噬作用，无论是否涉及SNAP 29。在这个项目的过程中收集的信息是必要的1）了解专业的吞噬细胞，如巨噬细胞如何消除细菌，2）确定分子目标，细胞内的细菌，如鼠伤寒沙门氏菌或结核分枝杆菌可能妥协，以逃避杀死，和3）指导新的战略，以打击传染病的发展。

DESCRIPTION (provided by applicant): Phagocytosis is critical for the elimination of invading pathogens, foreign particles, and dead cell bodies. Impairment of this process results in the development of disease, including infectious diseases. Surprisingly, despite the importance of this pathway, limited information is available regarding the mechanism(s) controlling phagosome maturation. In particular, the identity of the SNARE complexes controlling the fusion of the endocytic compartments with the phagosomes is incomplete. We have recently identified that the SNARE protein SNAP29 plays an early role in the killing of Escherichia coli by macrophages. Based on this discovery, we propose to address the hypothesis that SNAP29 forms fusogenic complex(es) with early endocytic SNAREs to control the early step of phagosome maturation. Using a unique multi-disciplinary approach, we will identify and characterize SNAP29-containing complexes involved in E. coli phagocytosis. In parallel, we will identify which early endocytic SNAREs play a role in E. coli phagocytosis, regardless of being involved with SNAP29. The information gathered during the course of this project is necessary to 1) understand how professional phagocytic cells such as macrophages eliminate bacteria, 2) identify molecular targets that intracellular bacteria such as Salmonella typhimurium or Mycobacterium tuberculosis may compromise to escape killing, and 3) guide the development of new strategies to fight infectious diseases.