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
More filters
Journal ArticleDOI
Cytohesin-associated scaffolding protein (CASP) is a substrate for granzyme B and ubiquitination
TL;DR: It is shown that CASP contains a conserved granzyme B cleavage site that could modify its intracellular localization and interaction with sorting nexin 27 and evidence that CASp is modified by ubiquitination is provided.
Journal ArticleDOI
Role of Caspases in the Cytotoxicity of NK-92 Cells in Various Models of Coculturing with Trophoblasts
Yu P Milyutina,V A Mikhailova,K M Pyatygina,E.S. Demidova,D A Malygina,T E Tertychnaia,A. V. Arutjunyan,D. I. Sokolov,S. A. Selkov +8 more
TL;DR: Changes in the content of caspases are examined and activation of these enzymes in Jeg-3 trophoblasts in various models of their coculturing with NK-92 cells are studied and it is demonstrated the necessity of direct contact between these cell populations for the activation of cspase-8 and caspase-3 in the trophobasts.
Journal ArticleDOI
How can Biology of Aging Explain the Severity of COVID-19 in Older Adults
Antonella Gallo,Erika Pero,Simona Pellegrino,N. Macerola,C Murace,Francesca Ibba,Maria Chiara Agnitelli,Francesco Landi,Massimo Montalto +8 more
TL;DR: Aging has been identified as one of the most relevant risk factors for poor outcomes in COVID-19 infection as mentioned in this paper and different mechanisms responsible for worse outcomes in the elderly have been proposed, which include the remodeling of immune system, the higher prevalence of malnutrition and sarcopenia, the increased burden of multimorbidity, and, to a lesser extent, the direct effects of age on the respiratory system and hormonal profile.
Journal ArticleDOI
Distinct patterns of cytolytic T-cell activation by different tumour cells revealed by Ca2+ signalling and granule mobilization.
Melissa A. Frick,Pierre Mouchacca,Grégory Verdeil,Yannick Hamon,Cyrille Billaudeau,Michel Buferne,Mathieu Fallet,Nathalie Auphan-Anezin,Anne-Marie Schmitt-Verhulst,Claude Boyer +9 more
TL;DR: In this paper, the ability of CTL to kill different tumour cell lines expressing the same cancer-germline gene P1A (Trap1a) was analyzed.
Journal ArticleDOI
Three Methods to Purify Leukocytes and RNA Quality Assessment.
TL;DR: The RBC lysis method should be recommended to biobanks for further research after it showed that leukocytes were purified using lymphocyte separation medium, optimized LSM method, or red blood cell lysis buffer (RBCLysis), and RNA quality met the basic requirements for downstream studies.
References
More filters
Journal ArticleDOI
The Immunological Synapse: A Molecular Machine Controlling T Cell Activation
Arash Grakoui,Shannon K. Bromley,Cenk Sumen,Mark M. Davis,Andrey S. Shaw,Paul M. Allen,Michael L. Dustin +6 more
TL;DR: Immunological synapse formation is now shown to be an active and dynamic mechanism that allows T cells to distinguish potential antigenic ligands and was a determinative event for T cell proliferation.
Journal ArticleDOI
Vacuolar ATPases: rotary proton pumps in physiology and pathophysiology.
TL;DR: The acidity of intracellular compartments and the extracellular environment is crucial to various cellular processes, including membrane trafficking, protein degradation, bone resorption and sperm maturation, and the V-ATPases represent attractive and potentially highly specific drug targets.
Journal ArticleDOI
The small GTPase rab5 functions as a regulatory factor in the early endocytic pathway.
Cecilia Bucci,Robert G. Parton,Ian H. Mather,Henk Stunnenberg,Kai Simons,Bernard Hoflack,Marino Zerial +6 more
TL;DR: It is concluded that rab5 is a rate-limiting component of the machinery regulating the kinetics of membrane traffic in the early endocytic pathway.
Journal ArticleDOI
Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, inhibits acidification and protein degradation in lysosomes of cultured cells.
TL;DR: Results suggest that the vacuolar type H(+)-ATPase plays a pivotal role in acidification and protein degradation in the lysosomes in vivo.
Journal ArticleDOI
Perforin Gene Defects in Familial Hemophagocytic Lymphohistiocytosis
Susan E. Stepp,Dufourcq-Lagelouse R,Françoise Le Deist,Françoise Le Deist,Sadhna Bhawan,Stéphanie Certain,Porunelloor A. Mathew,Jan-Inge Henter,Michael J. Bennett,Alain Fischer,Alain Fischer,Geneviève de Saint Basile,Vinay Kumar +12 more
TL;DR: In this paper, the coding regions of the perforin gene of eight unrelated 10q21-22-linked FHL patients revealed homozygous nonsense mutations in four patients and missense mutations in the other four patients.
Related Papers (5)
The structural basis for membrane binding and pore formation by lymphocyte perforin
Ruby H. P. Law,Natalya Lukoyanova,Ilia Voskoboinik,Ilia Voskoboinik,Tom T. Caradoc-Davies,Katherine Baran,Michelle A. Dunstone,Michelle A. Dunstone,Michael E. D'Angelo,Elena V. Orlova,Fasséli Coulibaly,Sandra Verschoor,Kylie A. Browne,Annette Ciccone,Michael J. Kuiper,Phillip I. Bird,Joseph A. Trapani,Joseph A. Trapani,Helen R. Saibil,James C. Whisstock,James C. Whisstock +20 more