Perforin pores in the endosomal membrane trigger the release of endocytosed granzyme B into the cytosol of target cells.
Jerome Thiery,Dennis Keefe,Dennis Keefe,Steeve Boulant,Steeve Boulant,Emmanuel Boucrot,Emmanuel Boucrot,Michael Walch,Michael Walch,Denis Martinvalet,Denis Martinvalet,Denis Martinvalet,Ing Swie Goping,R. Chris Bleackley,Tomas Kirchhausen,Tomas Kirchhausen,Judy Lieberman,Judy Lieberman +17 more
TLDR
It is shown that perforin formed pores in the gigantosome membrane, allowing endosomal cargo, including granzymes, to be gradually released.Abstract:
How the pore-forming protein perforin delivers apoptosis-inducing granzymes to the cytosol of target cells is uncertain. Perforin induces a transient Ca2+ flux in the target cell, which triggers a process to repair the damaged cell membrane. As a consequence, both perforin and granzymes are endocytosed into enlarged endosomes called 'gigantosomes'. Here we show that perforin formed pores in the gigantosome membrane, allowing endosomal cargo, including granzymes, to be gradually released. After about 15 min, gigantosomes ruptured, releasing their remaining content. Thus, perforin delivers granzymes by a two-step process that involves first transient pores in the cell membrane that trigger the endocytosis of granzyme and perforin and then pore formation in endosomes to trigger cytosolic release.read more
Citations
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DissertationDOI
Development of a platform technology for enhanced endo/lysosomal escape of targeted toxins by structurally specific oleanane saponins
Dissertation
Investigating the role of T-cells in chronic lymphocytic leukemia
TL;DR: This thesis addressed contradictory aspects of the role of T-cells in CLL by investigating the basis for immune dysfunction, and characterisation, involving mass spectrometry and HPLC, mapped T-cell specificity to a modified peptide (LLSY(3-tBu)FGTPT).
Journal ArticleDOI
Hemocompatible L-Type amino acid transporter 1 (LAT1)-Utilizing prodrugs of perforin inhibitors can accumulate into the pancreas and alleviate inflammation-induced apoptosis.
TL;DR: In this article, the distribution of two LAT1-utilizing prodrugs of investigational perforin inhibitors into the pancreas was explored after intraperitoneal (i.p., 30μmol/kg) bolus injection to mice.
Journal ArticleDOI
Immunohistochemical expression of perforin in lichen planus lesions.
Mohamed Abdelwahed Gaber,Alaa Hassan Maraee,Dalia Rifaat Alsheraky,Marwa Hussain Abdel Azeem +3 more
TL;DR: Accumulation of perforin + cells in the epidermis of LP lesions suggest a potential role of per forin in the apoptosis of basal keratinocytes.
Journal ArticleDOI
Bucket lists must be completed during cell death.
Kengo Nozaki,Edward A. Miao +1 more
TL;DR: In this paper , the authors define a set of effector programs before they die, which they define as a cellular "bucket list". These effector program are specific to the cell type, and mode and circumstances of death.
References
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