## 1 Introduction
### A Step towards Selective Inhibitors of Heterotrimeric G Proteins in Mammalian Cells
The tachycardia form is crescent-shaped and is usually found in intracellular clusters of 8 to 32 parasites and is the rapidly replicating form. The tachyzoites are responsible for tissue damage and the infection of the fetus in pregnant women. Tachyzoites develop into bradyzoites in particular in tissues of the muscle or the central nervous system (CNS) due to the host response immune reaction. Tachyzoites activate a potent host immune response that eliminates most of the parasites. Some tachyzoites, however, escape destruction and convert back into bradyzoites. Bradyzoites can be ingested in meat and when taken up by the human host they convert to tachyzoites. In _Toxoplasma gondii_ knowledge about signaling via G-protein mediated GPCRs is still rudimentary. Hitherto, there are no reports about canonical G-proteins in the _Toxoplasma_ database (http:/toxodb.org/toxo/) except for proteins containing repeats of motifs from the \(\beta\) subunits of canonical G-proteins. Hence, there is only one database entry from _Toxoplasma_ encoding a rhodopsin-like GPCR transmembrane domain protein. However, functional data for this receptor protein are still missing. Therefore, this database entry has to be considered critically. Moreover, there is a lack of knowledge about GTPases in _Toxoplasma gondii_. Apicomplexan parasites like _Toxoplasma gondii_ are dependent on the GPCR signaling network from the human host [45]. Secondly, parasite-induced host cell cytolysis has been suggested to be a two-step, Ca\({}^{2+}\)-dependent process [46]. This two-step process comprises ion loss of the host cell [47] and membrane poration. Previous results have implicated that three different parasitic proteins are involved in this process, i.e., a perforin-like protein [48], a kinase [49] and proteases that have not been further characterized [50]. However, recent data pinpoint [45] that host cell cytolysis is controlled by G\(\alpha\)q, phospholipase C (PLC), and protein kinase C (PKC). G\(\alpha\)q-coupled signaling results in protein kinase C (PKC)-mediated loss of the host cytoskeletal protein adducin and catastrophic influx of Ca\({}^{2+}\) through the cation channel TRPC6 which activates calpain to proteolyze the host cytoskeleton. Thus targeting proteins involved in host cell cytolysis might be an alternative, antiparasitic strategy that should be explored. Indeed, it was shown that a mammalian PKC-inhibitor G6976 (5,6,7,13-Tetrahydro-13-methyl-5-oxo-12\(H\)-indolol[2,3-\(a\)]pyrrolol[3,4-\(c\)]carbazole-12-propane-nitrile) limited _T. gondii_ parasitic burden in vivo in spleen [51] of the infected mice. In addition, a few host GTPases have been identified that play an important role in _Toxoplasma gondii_ infection. Interestingly, as an intracellular parasite _Toxoplasma_ replicates in a parasitophora vacuole (PV) that interacts with mammalian host organelles and intercepts Golgi Rab vesicles to acquire sphingolipids [52]. Thus, interrupting this vesicular pathway might be a successful strategy to prevent _Toxoplasma gondii_ infection. In _Toxoplasma gondii_ immunity related host GTPases (IRGs) are also recruited to pathogen-containing vacuoles, where they are important for their disruption resulting in cell-autonomous clearance. However, the suppressive mechanism was unclear. Meanwhile, it could be shown that Rab GDP dissociation inhibitor \(\alpha\) (RabGDI\(\alpha\)) acts as a suppressor of IFN-\(\gamma\)-induciblehost GTPases, such as Gbp2 and Irga6. RabGDI\(\alpha\) deficiency resulted in enhanced IFN-\(\gamma\)-mediated _T. gondii_ clearance in vitro and in vivo [53]. These observations can be attributed to a strong interaction between immunity-related host GTPases (IRG) and rhoptry (Rob5) pseudokineses expressed by the parasite [54] having two effects: (i) prevention of oligomerization of the IRG, and (ii) change in the orientation of two threonine residues that are targeted by the _Toxoplasma_ Ser/Thr kinases, ROP17 and ROP18.