Function of the haematopoietic GTPase RhoH in mast cell signalling

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RhoH is a haematopoiesis specific, GTPase-deficient member of the family of Rho proteins that acts as a regulator of JAK-STAT and NFκB signalling. We recently found that RhoH controls the expression levels of specific Toll like receptors (TLRs) that act as sensors of microbial components in the innate immune system. By this and other, so far uncharacterised pathways, RhoH expression levels influence TLR-mediated release of inflammatory cytokines from macrophages. It is known that RhoH has an impact on the signalling pathways involving Syk, STATs, NFkB and other Rho GTPases. However, very little is known about the exact molecular mechanisms of these signalling pathways. We aim to understand the mechanism of RhoH-mediated modulation of protein transport and TLR signalling on a molecular level. As a model system we will use bone marrow derived macrophages from wildtype and RhoHdeficient mice. We anticipate the results to be important in order to define mechanisms that might allow manipulating immune cells towards their desired, beneficial function. The project will investigate the regulation of TLR-induced immune signal transduction processes through RhoH leading to cytokine release and cellular functions such as phagocytosis.