Project Details
Projekt
Functional implications of the up-regulation of the RhoB protein induced by lethal toxin from Clostridium sordellii
Applicant
Professor Dr. Harald Genth
Subject Area
Cell Biology
Term
from 2003 to 2010
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 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 Programme
Priority Programmes
Participating Person
Professor Dr. Ingo Just
