Detailseite
Projekt
Funktionelle Auswirkungen der Expression des RhoB-Proteins durch das letale Toxin von Clostridium sordellii
Antragsteller
Professor Dr. Harald Genth
Fachliche Zuordnung
Zellbiologie
Förderung
Förderung von 2003 bis 2010
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5408684
The GTPase RhoA, which regulates actin cytoskeleton, cell cycle and gene transcription, is the preferred intracellular target of clostridial and staphylococcal C3-like exotoxins to be covalently modified by ADP-ribosylation. ADP-ribosylation of the Rho effector region is thought to result in inactive, "dead" Rho. However, the reported dominant negative action suggests full biological activity but rather in a negative functional mode. Based on the regulation of RhoA functions by GTPase cycle in combination with a compartimental cycling from cytosol to membranes and back, the aim of the planned project is to study the detailed functional outcome of ADP-ribosylation and the consequences for Rho signalling and for the cross-talk with other related GTPases: (i) the alteration of the subcellular localisation of ADP-ribosylated RhoA (cytosol - membrane distribution as well as lateral translocation of membrane-associated GTPases within membranous microdomains) (ii) regulation of the cytosolic GDI complex by ERM proteins, phospholipids, and peptides. The irreversible entrapment of Rho in the GDI complex by ADP-ribosylation may serve as a powerful tool within this study.
DFG-Verfahren
Schwerpunktprogramme
Beteiligte Person
Professor Dr. Ingo Just
