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Start of funding 01.07.2002
Rho proteins in endothelial barrier regulation
Prof. Dr. Detlev Drenckhahn
University of Würzburg
Institute of Anatomy and Cell Biology, Department II
Prof. Dr. Fitz Roy E. Curry
University of California, Davis
Physiology & Membrane Biology
The Rho family of small GTPases (Rho, Cdc42, Rac) plays a key role in the control of the actin cytoskeleton and in regulation of the barrier properties of the vascular endothelium that covers the inner side of blood vessels. The present collaboration between the California applicant (Prof. Curry, University of Davis, California) and the Bavarian applicant (Prof. Drenckhahn, University of Würzburg) is to understand in detail the molecular mechanisms underlying Rho protein-regulated modulation of endothelial permeability in vitro and in vivo. The laboratory of the Bavarian applicant has developed sophisticated cell biological and biophysical techniques (atomic force microscopy, laser tweezer, in vitro rheology systems), whereas the California group is one of the leading laboratories investigating vascular permeability in single perfused capillaries of mice and rats in vivo.
Final report:
The BaCaTeC has generously financed the collaboration of between the groups of Prof. Drenckhahn in Würzburg (BY) and Prof. Curry in Davis (CA). The financial support was spent for the project ’Rho proteins in endothelial barrier regulation’. The aim of the project was to establish a microvessel perfusion setup in Würzburg to allow parallel studies on endothelial barrier functions in vivo and in vitro. Therefore, Prof. Curry who is an outstanding specialist in the field of endothelial permeability research spent a short sabbatical leave in the laboratory of Prof. Drenckhahn to perform preliminary experiments and plan the project (ref.1). Afterwards, Dr. Waschke from the Drenckhahn group was sent to Davis for two stays to learn application and implementation of the perfusion technique. During these stays Dr. Waschke obtained data to further elucidate the role of Rho proteins in endothelial barrier regulation in vivo as well as the participating mechanisms. The results of this collaboration have been published in four further papers (ref.2-5). Back in Germany, funding by the IZKF (Interdisziplinäres Zentrum für Klinische Medizin) at the University of Würzburg helped to establish the setup for the in vivo permeability measurements which is almost completed at present. This setup is unique in continental Europe and will support cardiovascular research in Würzburg. To further characterize the role of Rho GTPases in permeability regulation, a grant proposal for funding by the Deutsche Forschungsgemeinschaft is in preparation. Finally, the contact persons whish to thank the BaCaTeC for generous support.
1. Adamson RH, Curry FE, Adamson G, Liu B, Jiang Y, Aktories K, Barth H, Daigeler A, Golenhofen N, Ness W, Drenckhahn D.: Rho and rho kinase modulation of barrier properties: cultured endothelial cells and intact microvessels of rats and mice. J Physiol 2002, 539:295-308.
2. Waschke J, Baumgartner W, Adamson RH, Zeng M, Aktories K, Barth H, Wilde C, Curry FE, Drenckhahn D.: Requirement of Rac activity for maintenance of capillary endothelial barrier properties. Am J Physiol Heart Circ Physiol 2004 Jan, 286(1):H394-401. Epub 2003 Sep 25.
3. Waschke J, Drenckhahn D, Adamson RH, Curry FE.: The role of adhesion and contraction in Rac 1-regulated endothelial barrier function in vivo and in vitro. Am J Physiol Heart Circ Physiol 2004 Aug, 287(2):H704-711. Epub 2004 Mar 25.
4. Waschke J, Drenckhahn D, Adamson RH, Barth H, Curry FE.: cAMP protects endothelial barrier functions by preventing Rac-1 inhibition. Am J Physiol Heart Circ Physiol 2004 Jul 22. Epub ahead of print.
5. Waschke, J., Curry, F.E., Adamson, R.H., Drenckhahn, D.: Regulation of actin dynamics is critical for endothelial barrier functions. Am J Physiol Heart Circ Physiol 2004 (in revision).