| Focusing on two intracellular SNARE proteins , Vti1b and syntaxin 6 ( Stx 6 ) , we show that they are up regulated in conjunction with increasing cytokine secretion in activated macrophages and that their levels are selectively titrated to accommodate the volume and timing of post Golgi cytokine trafficking . ^^^ Syntaxin 6 and Vti1b form a novel SNARE complex , which is up regulated in activated macrophages to facilitate exocytosis of tumor necrosis Factor alpha . ^^^ In macrophages , Vti1b and syntaxin 6 are localized on intracellular membranes and are present on isolated Golgi membranes and on Golgi derived TNFalpha vesicles budded in vitro . ^^^ By immunoprecipitation , we find that Vti1b and syntaxin 6 interact to form a novel intracellular Q SNARE complex . ^^^ Functional studies using overexpression of full length and truncated proteins show that both Vti1b and syntaxin 6 function and have rate limiting roles in TNFalpha trafficking and secretion . ^^^ |