Mechanistic peculiarities of activation-induced mobilization of cytotoxic effector proteins in human T cells.

摘要: It is widely accepted that cytotoxic T and NK cells store effector proteins including granzymes, perforin Fas ligand (FasL) in intracellular granules, often referred to as secretory lysosomes. Upon target cell encounter, these organelles are transported the immunological synapse, where they fuse with plasma membrane release soluble molecules expose transmembrane FasL on surface. We previously described two distinct species of vesicles differ size, morphology protein loading, most strikingly regarding granzyme B. now show signal requirements for mobilization one or other granule also substantially. report prestored can be mobilized independent extracellular Ca2+, whereas surface exposure lysosome-associated (Lamps; CD107a CD63) B calcium-dependent. The use selective inhibitors actin dynamics unequivocally points different transport mechanisms individual vesicles. While polymerization/dynamics inhibit appearance FasL, increase activation-induced CD107a, CD63 In contrast, inhibition actin-based motor myosin 2a facilitates FasL-, but impairs CD107a-, CD63- mobilization. From our data, we conclude granules differentially regulated respect signaling mechanisms. suggest a might 'sense' which it needs mobilize given context, thereby increasing efficacy while minimizing collateral damage.