title: Gamma interferon-induced guanylate binding protein 1 is a novel actin cytoskeleton remodeling factor.
abstract: Gamma interferon (IFN-γ) regulates immune defenses against viruses, intracellular pathogens, and tumors by modulating cell proliferation, migration, invasion, and vesicle trafficking processes. The large GTPase guanylate binding protein 1 (GBP-1) is among the cellular proteins that is the most abundantly induced by IFN-γ and mediates its cell biologic effects. As yet, the molecular mechanisms of action of GBP-1 remain unknown. Applying an interaction proteomics approach, we identified actin as a strong and specific binding partner of GBP-1. Furthermore, GBP-1 colocalized with actin at the subcellular level and was both necessary and sufficient for the extensive remodeling of the fibrous actin structure observed in IFN-γ-exposed cells. These effects were dependent on the oligomerization and the GTPase activity of GBP-1. Purified GBP-1 and actin bound to each other, and this interaction was sufficient to impair the formation of actin filaments in vitro, as demonstrated by atomic force microscopy, dynamic light scattering, and fluorescence-monitored polymerization. Cosedimentation and band shift analyses demonstrated that GBP-1 binds robustly to globular actin and slightly to filamentous actin. This indicated that GBP-1 may induce actin remodeling via globular actin sequestering and/or filament capping. These results establish GBP-1 as a novel member within the family of actin-remodeling proteins specifically mediating IFN-γ-dependent defense strategies.
authors.affiliation: Division of Molecular and Experimental Surgery, University Medical Center Erlangen, Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Ostler
authors.forename: Nathalie
authors.initials: N
authors.lastname: Britzen-Laurent
authors.forename: Andrea
authors.initials: A
authors.lastname: Liebl
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Naschberger
authors.forename: Günter
authors.initials: G
authors.lastname: Lochnit
authors.forename: Markus
authors.initials: M
authors.lastname: Ostler
authors.forename: Florian
authors.initials: F
authors.lastname: Forster
authors.forename: Peter
authors.initials: P
authors.lastname: Kunzelmann
authors.forename: Semra
authors.initials: S
authors.lastname: Ince
authors.forename: Verena
authors.initials: V
authors.lastname: Supper
authors.forename: Gerrit J K
authors.initials: GJ
authors.lastname: Praefcke
authors.forename: Dirk W
authors.initials: DW
authors.lastname: Schubert
authors.forename: Hannes
authors.initials: H
authors.lastname: Stockinger
authors.forename: Christian
authors.initials: C
authors.lastname: Herrmann
authors.forename: Michael
authors.initials: M
authors.lastname: Stürzl
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000201:enzymology; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D058105:Polymerization; D011485:Protein Binding; D025941:Protein Interaction Mapping; D055503:Protein Multimerization; D021381:Protein Transport; D022502:Stress Fibers / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D000199:Actins; C490287:GBP1 protein, human; D007371:Interferon-gamma; D019204:GTP-Binding Proteins