THE ROLE OF CASP IN NATURAL KILLER CELL IMMUNE FUNCTION

Abstract

Natural Killer (NK) cells are highly mobile, specialized sub-populations of lymphocytic cells that survey their host to identify and eliminate infected or tumor cells. They are one of the key players in innate immunity and do not need prior activation through antigen recognition to deliver cytotoxic packages and release messenger chemicals to recruit immune cells. Cytohesin associated scaffolding protein (CASP) is a lymphocyte specific adaptor protein that forms complexes with vesicles and sorting proteins including SNX27 and Cytohesin-1. In this study I show that by using stably integrated shRNA, CASP has a direct role in the secretion of messenger cytokines including IFN-γ, and impedes NK cell motility and ability to kill tumor cells. I also show that CASP is post-translationally modified by ubiquitination and cleavage by granzyme B. CASP is an essential and multi-faceted protein, which has a very diverse role in NK cell specific immune functions.