Lack of appropriate animal models that closely recapitulate the human disease further complicates the problem. It is well known that SAg bind more effectively with human MHC class II molecules than to mouse MHC class II molecules. Therefore, we have established that unlike the conventional mice strains, mice that transgenically express the HLA-DR or HLA-DQ molecules in the absence of any endogenous MHC class II molecules, mount a robust immune response to bacterial superantigens and are readily susceptible to TSS without the use of any sensitizing agents such as D-galactosamine or bacterial lipopolysaccharide. TSS seen in HLA class II transgenic mice also closely mimics the human disease. Therefore, we used HLA-DR3 transgenic mice to evaluate the role of IFN-c in the pathogenesis of TSS. In eukaryotic cells, Rho family small GTPases play a crucial role in polarized growth through reorganization of the actin cytoskeleton and the regulation of secretory vesicle transport. Although detailed knowledge is available on the role of Rho family proteins in the actin cytoskeleton, various functional aspects of the Rho signaling pathway with regard to membrane trafficking are relatively unknown. Recently, Rho GTPase proteins have been attracting increasing attention for their role in exocytosis. In mast cells, recombinant Rac and Rho proteins stimulate the exocytosis of secretory granules. RhoD and RhoB are localized in endocytic vesicles, and RhoD regulates endosome dynamics through Diaphanousrelated Formin and Src tyrosine kinase. In the budding yeast Saccharomyces cerevisiae, Rho3 appears to influence cell growth by regulating polarized secretion as well as the actin cytoskeleton by interacting with Exo70 and Myo2. Thus, the Exo70 subunit of the exocyst is an effector of Rho3 in polarized exocytosis. In the fission yeast Schizosaccharomyces pombe, Rho3 is implicated in polarized cell growth through both Formin and by modulating exocyst function. However, little is known about the role of Rho3 in Golgi/endosome function in fission yeast. We previously identified a GDC-0879 mutant allele of the apm1+ gene that encodes a m1 subunit of the adaptor protein complex, and characterized the role of Apm1 in Golgi/endosome trafficking, vacuole fusion, and secretion in fission yeast. In order to gain further insight into the function of Apm1, we screened for a multi-copy suppressor of apm1-1 mutant cells and identified Rho3, a member of the Rho GTPase family. In the present study, we show that in addition to its well-known role for the regulation of exocytosis, Rho3 plays an important role in Golgi/endosome trafficking. Notably, Rho3 forms a complex with Apm1 and with other subunits of the RG7204 clinical trial clathrin-associated adaptor protein-1 complex and suppresses the deletion cells of all the subunits of the AP-1 complex. To the best of our knowledge, the present study provides the first evidence of a direct link between the small GTPase Rho3 and the clathrin-associated adaptor protein-1 in membrane trafficking.