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
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Dissertation
Cholesterol-Dependent Cytolysins and Perforin: Similar Pore-Forming Mechanisms in Pathogenic Attack and Human Immune Defense
TL;DR: This PhD work underlines two physiological structures which are involved in several ways, more than merely by disrupting membrane integrity, in pathogenic attack (bacterial CDCs proteins as well as in immune response (human Perforin proteins).
Journal ArticleDOI
Muscle fiber necroptosis in pathophysiology of idiopathic inflammatory myopathies and its potential as target of novel treatment strategy
TL;DR: In this paper , the authors discuss the potential treatment strategy targeting muscle fiber necroptosis in IIMs and reveal that not only alleviates muscle inflammation but also improves muscle weakness without increment of opportunistic infection.
References
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