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

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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.