The Role of Rho GTPases, Rac1 and Rac2, in Mast Cell Exocytosis

Alicia Baier
2012
Mast cells are tissue-resident immune cells that undergo exocytosis upon activation, releasing potent immunoregulatory molecules that initiate inflammatory responses. Here, I investigated the role of the hematopoietic specific Rho GTPase, Rac2, and the ubiquitous, Rac1, on mast cell exocytosis. Our hypothesis is that FcRI-mediated mast cell exocytosis is differentially regulated by Rac1 and Rac2 GTPases. Three experimental systems were used to investigate their roles in mast cell function;
more » ... cell function; Rac2 knockout mice, Rac1 and Rac2 siRNA knockdown, and treatment with the Rac inhibitor, EHT-1864. My results suggest that Rac1 and Rac2 regulate multiple stages of FcRI-mediated response in mast cells. I found that calcium flux and exocytosis were Rac1 and Rac2dependent processes. My data suggests that Rac1 and Rac2 regulate exocytosis through a convergent pathway but regulate calcium flux through alternate pathways. Moreover, I found that Rac2 does not regulate actin remodelling, thereby suggesting this may be a Rac1-mediated process. CHAPTER 1
doi:10.7939/r3804v fatcat:osp5axxk3resljqyac62pdtnoy