Role of the WAVE-complex in the hematopoietic System

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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.