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

• Author / Creator

  Baier, Alicia

• 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(epsilon)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; 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(epsilon)RI-mediated response in mast cells. I found that calcium flux and exocytosis were Rac1 and Rac2-dependent 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, suggesting this may be a Rac1-mediated process.

• Subjects / Keywords

  • Rac1 and Rac2 GTPases
  • Mast cell
  • Exocytosis

• Graduation date

  Spring 2012

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3804V

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.