Role of the WAVE-complex in the hematopoietic System

WAVE 复合体在造血系统中的作用

• 批准号: 170443782
• 负责人: Professor Michael Sixt
• 金额: --
• 依托单位: Helmholtz-Zentrum für Infektionsforschung (HZI)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/170443782?language=en
• 关键词: Role; WAVE; complex; hematopoietic; System

Cytoplasm and extracellular space are separated by the plasma membrane, encasing a dynamic, force generating actin microfilament network. This composite barrier is spiked with transmembrane receptors and capable of transducing signals from the outside of the cell to the cytoplasm. Cell motility, adhesion, migration but also phagocytosis depend on the formation of actin dependent protrusions, the most prominent of which are filopodia and lamellipodia. More recently, cell surface blebbing as yet another form of motile behaviour came into focus, although it remained unclear to what extent it requires active actin assembly. In contrast, it is well established that the formation of lamellipodia and filopodia relies on the catalysed polymerisation of actin filaments at the advancing cell front and that ignition of the process of protrusion involves signalling to the submembraneous microfilament network. Main goal of the this project is to understand when and where motogenic signalling to the WAVE-complex is required for different types of motile behaviour. This shall be achieved by the characterisation of a novel knockout mouse model that we recently established. Conditional targeting of the gene hem1 allows for cell- and developmental stage-specific depletion of the entire WAVE-complex from different types of hematopoetic cells. WAVE-complex is an actin polymerase established to be absolutely required for lamellipodium protrusion. Thus, using this system we can unambiguously clarify the role of WAVE-complex-mediated actin assembly in phenotypically different motile behaviours.

细胞质和细胞外间隙被质膜隔开，包围着一个动态的、产生力量的肌动蛋白微丝网络。这种复合屏障充满了跨膜受体，能够将信号从细胞外部传递到细胞质。细胞的运动、黏附、迁移以及吞噬作用都依赖于肌动蛋白依赖性突起的形成，其中最突出的是丝足和片脂。最近，细胞表面起泡作为另一种形式的运动行为开始受到关注，尽管尚不清楚它在多大程度上需要主动肌动蛋白组装。相反，板脂和丝足的形成依赖于推进细胞前端肌动蛋白细丝的催化聚合，而突起过程的点燃涉及到向膜下微丝网络发出信号。这个项目的主要目标是了解不同类型的运动行为需要在何时何地向波复合体发送自动机信号。这将通过我们最近建立的一种新的基因敲除小鼠模型来实现。有条件地靶向基因hem1可以使不同类型造血细胞的整个波复合体在细胞和发育阶段特异性地耗尽。波-复合体是一种肌动蛋白聚合酶，被认为是片状磷脂突起所必需的。因此，使用这个系统，我们可以明确地阐明波-复合体介导的肌动蛋白组装在不同的表型运动行为中的作用。