Role of rab2a, rab5a, rab17 and rab18 in effector function of cytotoxic cells

• Grant number: 11/20352-3
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: January 01, 2012
• End date: August 31, 2015
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: João Gustavo Pessini Amarante Mendes
• Grantee: Narciso Junior Vieira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 13/16550-0 - Short term training abroad on lymphocytic Choriomeningitis virus, BE.EP.DD

Abstract

Cytotoxic T lymphocytes and Natural Killer cells are important components of the immune system that operate against intracellular pathogens as well as tumor cells. One of the main mechanisms by which these cells exert their cytotoxic activity is through the secretion of lytic granules, which are hybrid organelles specialized in the release of cytotoxic effector molecules, such as perforin and granzymes. The complete knowledge of the machinery involved in the movement of secretory granules is critical, since defects in intracellular trafficking pathways form the basis of a large number of conditions that trigger fatal diseases. A family of proteins called Rabs has emerged in studies of the processes of intracellular trafficking of vesicles and has been related to mechanisms that regulate signal transduction and cellular processes such as differentiation, proliferation, nuclear aggregation and cytoskeletal remodeling. Although important functions of Rabs in intracellular traffic of vesicles in many different cell types have been described, there are few reports in the literature about the role of these proteins in the movement of cytotoxic granules in NK cells and cytotoxic T lymphocytes. Proteomic studies performed by our group identified for the first time the presence of Rab2a, Rab5a, Rab17 and Rab18 in cytotoxic granules of NK cells and cytotoxic T lymphocytes. For this reason, these proteins constitute the object of this project, which will consist in validating their presence in the granules of cytotoxic cells and identifying their roles in the secretion of cytotoxic granules. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

VIEIRA, Narciso Junior. Role of RAB2A, RAB5A, RAB17 andRAB18 in effector functions of cytotoxic cells.. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.