Characterisation of N-WASP-defective-cells and N-WASP-interacting proteins

• Antragsteller: Professor Dr. Jürgen Wehland (†)
• Fachliche Zuordnung: Zellbiologie
• Förderung: Förderung von 1998 bis 2008
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5154460

The Act A protein of Listeria monocytogenes is sufficient to induce actin filament formation on the bacterial surface within infected host cells, leading to intracellular bacterial movement. Thus this intracellular bacterial pathogen serves as a simplified model for the analysis of actin-based cell motility. The ActA protein harbors several sites which interact with microfilament-associated proteins that are involved in the process of actin filament formation, including thus far the Ena/VASP protein family and the Arp 2/3 complex. Therefore the identification of eucaryotic proteins which harbor ActA-related motifs should help to elucidate the process of actin filament formation. During the first year of funding we identified an eucaryotic protein that is restricted to hematopoietic cells and that harbors an Ena/VASP, i.e., EVH1 domain binding motif and interacts in vivo and in vitro with members of the Ena/VASP protein family. This protein localizes to lamellipodia of spreading platelets and is recruited to contact sites between T-cells and anti-CD3 coated beads, mimicking antigen presenting cells (APCs), during T-cell activation. Therefore one aim of this proposal is to characterize this Ena/VASP binding protein in detail in order to elucidate its role in cytoskeletal reorganization, a prerequisite for T-cell migration and activation. The second aim of this proposal is to apply a similar approach to non-hematopoietic cells to identify the key players involved in actin-based extension of lamellipodia.

• DFG-Verfahren: Schwerpunktprogramme
• Teilprojekt zu: SPP 1049: Molekulare Steuerungsmechanismen der Zellwanderung
• Beteiligte Person: Professor Dr. Klemens Rottner