A Role for the Phagosome in Cytokine Secretion

Science 310: 1492-1495, 2005

Speaker: 林建達                 Time: 2006/05/17 14:00-15:00

Commentator: 林秋烽 博士       Place: Room 601

Abstract:

Membrane traffic in activated macrophages is required for two critical events in innate immunity: proinflammatory cytokine secretion and phagocytosis of pathogens. This paper describes a joint trafficking pathway linking both actions, which may economize membrane transport and augment the immune response. Soluble N-ethylmaleimide–sensitive factor (NSF) attachment receptor, SNARE is the major player in the final stage of the docking and the subsequent fusion of diverse vesicle-mediated transport events. SNAREs can be classified into v-SNAREs (associated with the vesicle/container) and t-SNAREs (associated with the target compartment). Vesicle-associated membrane protein 3 (VAMP3) is one of the v-SNARE proteins. Tumor necrosis factor α (TNFα) is trafficked from the Golgi to the recycling endosome (RE), where VAMP3 mediates its delivery to the cell surface at the site of phagocytic cup formation. Fusion of the RE at the cup simultaneously allows rapid release of TNFα and expands the membrane for phagocytosis. The secretory pathway for the trafficking of the newly synthesized transmembrane form of TNFα to the cell surface is unknown. In this paper, specific vesicular machinery that functions in this pathway has been identified.

References:

1. Hong,W, SNAREs and traffic. Biochim. Biophys. Acta 1744, 120 (2005)..

2. Allen L. A., Yang C., Pessin J. E., Rate and extent of phagocytosis in macrophages lacking vamp3, J. Leukoc. Biol. 72, 217 (2002).