New proteins responsible for the interaction between phagosomes and F-Actin and their role in macrophage function

负责吞噬体和 F-肌动蛋白之间相互作用的新蛋白质及其在巨噬细胞功能中的作用

• 批准号: 12775306
• 负责人: Privatdozent Dr. Sergei A. Kuznetsov
• 金额: --
• 依托单位: Institut für Biowissenschaften (IfBi)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/12775306?language=en
• 关键词: New; proteins; responsible; interaction; between

Phagosome interaction with the cytoskeleton plays a key role in phagosome maturation which leads to pathogen killing. We developed an in vitro binding assay to analyze how in model system latex bead loaded phagosomes bind to F-actin. Three cytoplasmic factors were found to be involved in the interactions between F-actin and phagosomes. One factor responsible for the ATP-dependent binding was identified as myosin Va. This myosin bound to phagosomes was shown to delay microtubule-dependent retrograde phagosome movement toward the cell center. The goal of this proposal is to identify the other two factors: a high molecular weight (> 600 kDa) actin-binding protein (HMWABP) responsible for the ATP-independent binding of LBPs to F-actin, and a small (s 15-25 kDa) cytosolic protein that inhibits association of both myosin Va and HMWABP with phagosomes. The role of myosin V and the newly identified factors in the regulation of phagosome interaction with F-actin and in phagosome biogenesis will then be analyzed in vivo.

吞噬体与细胞骨架的相互作用在吞噬体成熟中起关键作用，从而导致病原体的杀灭。我们开发了一种体外结合试验来分析在模型系统中乳胶珠负载的吞噬体如何与F-肌动蛋白结合。三个细胞质因子被发现参与F-肌动蛋白和吞噬体之间的相互作用。一个负责ATP依赖性结合的因子被鉴定为肌球蛋白Va。这种与吞噬体结合的肌球蛋白被证明可以延迟微管依赖性的吞噬体向细胞中心的逆行运动。该提议的目标是鉴定另外两种因子：负责LBP与F-肌动蛋白的ATP非依赖性结合的高分子量（> 600 kDa）肌动蛋白结合蛋白（HMWABP），以及抑制肌球蛋白Va和HMWABP与吞噬体结合的小的（s 15-25 kDa）胞质蛋白。肌球蛋白V和新发现的因子在吞噬体与F-肌动蛋白的相互作用和吞噬体生物发生的调节中的作用将在体内进行分析。