Protecting a serial killer: pathways for perforin trafficking and self-defence ensure sequential target cell death
Jamie A Lopez, Amelia J Brennan, James C Whisstock, Ilia Voskoboinik, Joseph A Trapani
TRENDS IN IMMUNOLOGY | ELSEVIER SCI LTD | Published : 2012
Considerable progress has been made in understanding how cytotoxic lymphocytes use the highly toxic pore-forming protein perforin to eliminate dangerous cells, while remaining refractory to lysis. At least two mechanisms jointly preserve the killer cell: the C-terminal residues of perforin dictate its rapid export from the endoplasmic reticulum (ER), whose milieu otherwise favours pore formation; perforin is then stored in secretory granules whose acidity prevent its oligomerisation. Following exocytosis, perforin delivers the proapoptotic protease, granzyme B, into the target cell by disrupting its plasma membrane. Although the precise mechanism of perforin/granzyme synergy remains controve..View full abstract
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J.A.L. and A.J.B. are both supported by a NH&MRC Postdoctoral Training Fellowship. J.C.W., I.V. and J.A.T. are supported by fellowships and/or grants from the NH&MRC. J.C.W. is an Australian Research Council Federation Fellow.