Role of beta1-integrins and their intracellular and extracellular linker molecules for G protein-coupled signaling cascades

• Antragsteller: Professor Dr. Wilhelm Bloch
• Fachliche Zuordnung: Dermatologie
• Förderung: Förderung von 2002 bis 2008
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5394286

Aim of the proposal is to elucidate the role of b1-integrins for pertussis toxin-sensitive G protein-coupled signaling pathways. The key finding motivating this investigation is a selective muscarinic signaling defect in b1 integrin (-/-) cardiomyocytes due to displacement of Gi. The relevance of this defect will be investigated in endothelial cells, where Gi-coupled signaling represents a key event for endothelial cell function. We are planning to analyze functional coupling of the other pertussis toxin sensitive G protein Go in ES cell-derived neuronal cells. To understand the significance of the cytoskeletal integrity for Gi/o signaling, reconstitution experiments will be performed, where G protein subunits are reintroduced into the cytosol via the patch pipette and recovery of function tested in b1 integrin (-/-) ES cell-derived cells. The significance of intact extracellular anchorage for G protein-coupled signaling is evaluated in b1 integrin (-/-) cells, where addition of laminin rescues defective basal membrane formation. The proposed study is aimed to clarify the molecular role of b1 integrins in membrane delimited signal transduction processes.

• DFG-Verfahren: Schwerpunktprogramme
• Teilprojekt zu: SPP 1086: Genetische und molekulare Analyse von Basalmembranen und Basalmembranverankerung
• Beteiligte Person: Professor Dr. Bernd Fleischmann