gms | German Medical Science

125. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

22. - 25.04.2008, Berlin

Characterisation of the secretion pathway of Guanylate Binding Protein-1

Meeting Abstract

  • corresponding author N. Meyer - Division of Molecular and Experimental Surgery, Department of Surgery, University of Erlangen-Nuremberg
  • E. Naschberger - Division of Molecular and Experimental Surgery, Department of Surgery, University of Erlangen-Nuremberg
  • N. Gonin-Laurent - Division of Molecular and Experimental Surgery, Department of Surgery, University of Erlangen-Nuremberg
  • W. Hohenberger - Department of Surgery, University of Erlangen-Nuremberg
  • M. Stürzl - Division of Molecular and Experimental Surgery, Department of Surgery, University of Erlangen-Nuremberg

Deutsche Gesellschaft für Chirurgie. 125. Kongress der Deutschen Gesellschaft für Chirurgie. Berlin, 22.-25.04.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. Doc08dgch9330

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgch2008/08dgch392.shtml

Veröffentlicht: 16. April 2008

© 2008 Meyer et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Introduction: The guanylate binding protein-1 (GBP-1) belongs to the family of large GTPases which consists of 7 highly homologous proteins. The best characterized member of this family is GBP-1. The crystal structure of GBP-1 shows that the protein consists of two different domains, a N-terminal globular domain and a C-terminal helical domain. GBP-1 can be induced by interferon (IFN)-γ in many different cell types in vitro but is almost exclusively expressed in endothelial cells (EC) in vivo. In EC GBP-1 shows a granular cytoplasmic distribution which is a characteristic feature of secreted proteins.

Materials and methods: Recombinant expression of different proteins in primary EC, immunoprecipitation, immunoblotting, ELISA

Results: We found that GBP-1 is secreted from IFN-γ-stimulated EC in a time and concentration dependent manner. GBP-1 secretion was inhibited with glyburide, an inhibitor of alternative secretion pathways via ABC-transporters, but not with monensin, an inhibitor of the classical secretion pathway. GBP-1 was selectively secreted from EC but not from fibroblasts, smooth muscle cells or keratinocytes. Furthermore, GBP-1 was the only secreted member of the GBP-family. Important motifs regulating the secretion of GBP-1 were identified via expression of different mutants of GBP-1 in EC.

Conclusion: GBP-1 is the first GTPase which was found to be secreted from eukaryotic cells. It will be of high interest to investigate the extracellular functions of secreted GBP-1 in the future.