Neutrophil direction sensing and superoxide production linked by the GTPase-activating protein GIT2

Speaker: 呂秀菱                    Time: Sep. 20. 2006. 15:10- 16:00

Commentator: 謝奇璋 醫師           Room: 601

Abstract:

    In innate immunity, neutrophils are often first activated and move toward the inflammatory or infected sites. During the chemotaxis, some of immune response has already occurred, such as antimicrobial agent production including superoxide anion which is one of reactive oxygen species (ROS) quickly produced by NADPH oxidase¹. Although the molecular mechanisms underlying both chemotaxis and superoxide anion production in neutrophils have been studied extensively, the molecules and mechanisms that connect these two processes remain mostly unknown. Here the authors found that GTPase-activating protein GIT2 activated many of G protein-coupled receptor (GPCR) downstream molecules for chemotactic direction sensing². At the same time, negative regulation of Arf activity (NADPH oxidase activator) by GIT2 was reduced, and the superoxide production was increased. In addition to Arf, Rac which is another NADPH oxidase activator could be activated by aPIX, a guanine nucleotide–exchange factor and GPCR downstream molecule, and assisted with GIT2 binding. GIT2 was important for neutrophils to correct recruitment ofGPCR downstream molecules and NADPH oxidase subunits forward chemoattractants, and the data showed immunodeficiency in GIT2-deficient mice. The authors therefore established a linking function of GIT2 between chemotaxis and superoxide production in neutrophils.

References:

1. Cross, A.R. & Segel, A.W. The NADPH oxidase of professional phagocytes: prototype of the NOX electron transport chain systems. Biochim. Biophys. Acta, 1657: 1-22, 2004.

2. Mazaki, Y. et al. Neutrophil direction sensing and superoxide production linked by the GTPase-activating protein GIT2. Nat. Immunol. 7: 724-731,  2006.