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
Developing peptide vaccines for breast cancer
TL;DR: A method for enhancing the immunogenicity of these three HLA-A*0201 (HLA-A2)-restricted breast cancer epitopes was described, and it was found that the BST-2 APL was capable of generating a T-cell response of greater magnitude, and that was also better able to kill breast cancer cells when compared to the corresponding BST- 2 WT peptide.
Dissertation
Characterization of KIR2DS1+ decidual Natural Killer cells in healthy and viral/bacterial – infected human pregnancy
TL;DR: Tese de doutoramento em Biociencias, na area de especializacao de Biologia Celular e Molecular, apresentada ao Departamento de Ciencias da Vida da Faculdade de Cientícias e Tecnologia da Universidade de Coimbra,
Dissertation
TCR signals in the identity and function of mature NKT and regulatory T cells
TL;DR: It is proposed that peripheral NKT cells become unresponsive to and thus are independent of their autoreactive TCR, which is largely Dispensable for Mature NKT Cell Biology.
References
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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.
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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.
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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.
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