The role of the human guanylate-binding protein 1 in the formation and trafficking of phagosomes and other pathogen containing membrane compartments

• Antragsteller: Dr. Gerrit Praefcke
• Fachliche Zuordnung: Zellbiologie
• Förderung: Förderung von 2011 bis 2016
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 198174579

Guanylate-binding proteins (GBPs) belong to the dynamin superfamily of large GTPases which are involved in various cellular membrane remodelling events. GBPs share biochemical and functional properties with the dynamin-like Mx proteins as well as the p47 immunity-related GTPases (IRGs), such as a strong induction by interferons, anti-pathogenic activity, membrane association, weak nucleotide binding and an assembly-stimulated increase of the intrinsic GTPase activity. In cells, endogenous human GBP1 shows a vesicular staining pattern and relocalises to the Golgi complex upon activation by aluminium fluoride. This process requires posttranslational lipid modification of the C-terminus of hGBP1, an unknown interferon inducible factor and a conformation change which is induced by binding of aluminium fluoride to the active site. Recently, we have been able to recapitulate this membrane recruitment in vitro with recombinant lipid-modified hGBP1 produced by a combination of co-expression systems and in vitro modification reactions. Moreover, we found cellular hGBP1 at newly forming phagosomes independently of its activation state and of other interferon-stimulated factors. Therefore, we want identify the phagosomal factors responsible for this recruitment and also the impact of hGBP1 on the maturation and trafficking of phagosomes and other pathogen-containing membrane compartments.

• DFG-Verfahren: Schwerpunktprogramme
• Teilprojekt zu: SPP 1580: Intracellular compartments as places of pathogen-host-interactions
• Beteiligte Person: Professor Dr. Thomas Kufer