Perforin pores in the endosomal membrane trigger the release of endocytosed granzyme B into the cytosol of target cells

Jerome Thiery ,et al.Nat Immunol. 19;12(8):770-7(2011)

Speaker:Shun-Yi Chien (錢舜益)                                   Time:14:10~15:00,Nov.23,2011

Commentator: Hsiao-Sheng Liu (劉校生老師)             Place:Room 601

Abstract

Cytotoxic T cell and natural killer(NK) cells eliminate virus-infected or tumor by releasing the cytotoxic granules [1].The serine protease,granzyme in the granule can induce apoptosis through caspase-3 after they are released into the target cell cytosol by the pore-forming perforin.But the way that perforin deliversgranzyme to the cytosol of target cell is uncertain.During granule-mediated cell death,perfor cause Ca2+ influx and that will induce endocytosis by damaged-membrane response[2]. Moreover enlarged vesicles,called gigatosomes are form that contain perforin and granzymes.The aim of this study was to figure out how enlarged vesicles form and how granzyme are release from them .The study find that perforin formd pores in the gigatosome membrane,causing granzyme to be released. Thus,perforin make granzyme release by two-step process.Fist,the pore in the cell membrane that trigger the endocytosis of granzyme andperforin.Secondly,the pore form in gigatosome to make granzyme release into cytoplasma.

References

1.     Stinchcombe, J.C., Bossi, G., Booth, S. & Griffiths, G.M. The immunological synapse of CTL contains a secretory domain and membrane bridges. Immunity 15, 751–761 (2001).

2.     Keefe, D. et al. Perforin triggers a plasma membrane-repair response that facilitates CTL induction of apoptosis. Immunity 23, 249–262 (2005).