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Blood, 1 March 2005, Vol. 105, No. 5, pp. 2049-2058. Prepublished online as a Blood First Edition Paper on November 4, 2004; DOI 10.1182/blood-2004-06-2180. This Article Full Text (PDF) All Versions of this Article: 2004-06-2180v1 105/5/2049    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kurschus, F. C Articles by Jenne, D. E Search for Related Content PubMed PubMed Citation Articles by Kurschus, F. C Articles by Jenne, D. E Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 14, 2004 Accepted October 24, 2004 Membrane receptors are not required to deliver granzyme B during killer cell attack Florian C Kurschus*, Roxana Bruno, Edward Fellows, Christine S Falk, and Dieter E Jenne Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, Planegg-Martinsried, Germany Institute for Molecular Immunology, GSF, Munich, Germany * Corresponding author; email: kurschus{at}neuro.mpg.de. Granzyme B (GzmB), a serine protease of cytotoxic T-cells and natural killer (NK) cells induces apoptosis by caspase activation after crossing the plasma membrane of target cells. The mechanism of this translocation during killer cell attack, however, is not understood. Killer cells release GzmB and the membrane-disturbing perforin at the contact site after target recognition. Receptor-mediated import of glycosylated GzmB and release from endosomes was suggested, but the role of the cation independent mannose 6-phosphate receptor was recently refuted. Using recombinant nonglycosylated GzmB, we observed binding of GzmB to cellular membranes in a cell type dependent manner. The basis and functional impact of surface binding was clarified. GzmB binding was correlated with the surface density of heparan sulfate chains, was eliminated upon treatment of target cells with heparinase III or sodium chlorate and was completely blocked by an excess of catalytically inactive GzmB or GzmK. Although heparan sulfate bound GzmB was taken up rapidly into intracellular lysosomal compartments, neither of the treatments had an inhibitory influence on apoptosis induced by externally added streptolysin O and GzmB or by natural killer cells. We conclude that membrane receptors for GzmB on target cells are not crucial for killer cell mediated apoptosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Korkmaz, A. Kuhl, B. Bayat, S. Santoso, and D. E. Jenne A Hydrophobic Patch on Proteinase 3, the Target of Autoantibodies in Wegener Granulomatosis, Mediates Membrane Binding via NB1 Receptors J. Biol. Chem., December 19, 2008; 283(51): 35976 - 35982. [Abstract] [Full Text] [PDF] F. C. Kurschus, E. Fellows, E. Stegmann, and D. E. Jenne Granzyme B delivery via perforin is restricted by size, but not by heparan sulfate-dependent endocytosis PNAS, September 16, 2008; 105(37): 13799 - 13804. [Abstract] [Full Text] [PDF] E. Fellows, S. Gil-Parrado, D. E. Jenne, and F. C. Kurschus Natural killer cell-derived human granzyme H induces an alternative, caspase-independent cell-death program Blood, July 15, 2007; 110(2): 544 - 552. [Abstract] [Full Text] [PDF] T. Wang, R. Allie, K. Conant, N. Haughey, J. Turchan-Chelowo, K. Hahn, A. Rosen, J. Steiner, S. Keswani, M. Jones, et al. Granzyme B mediates neurotoxicity through a G-protein-coupled receptor FASEB J, June 1, 2006; 20(8): 1209 - 1211. [Abstract] [Full Text] [PDF] K. Veugelers, B. Motyka, I. S. Goping, I. Shostak, T. Sawchuk, and R. C. Bleackley Granule-mediated Killing by Granzyme B and Perforin Requires a Mannose 6-Phosphate Receptor and Is Augmented by Cell Surface Heparan Sulfate Mol. Biol. Cell, February 1, 2006; 17(2): 623 - 633. [Abstract] [Full Text] [PDF] C. H. Bird, J. Sun, K. Ung, D. Karambalis, J. C. Whisstock, J. A. Trapani, and P. I. Bird Cationic Sites on Granzyme B Contribute to Cytotoxicity by Promoting Its Uptake into Target Cells Mol. Cell. Biol., September 1, 2005; 25(17): 7854 - 7867. [Abstract] [Full Text] [PDF] S. M. Raja, S. S. Metkar, S. Honing, B. Wang, W. A. Russin, N. H. Pipalia, C. Menaa, M. Belting, X. Cao, R. Dressel, et al. A Novel Mechanism for Protein Delivery: GRANZYME B UNDERGOES ELECTROSTATIC EXCHANGE FROM SERGLYCIN TO TARGET CELLS J. Biol. Chem., May 27, 2005; 280(21): 20752 - 20761. [Abstract] [Full Text] [PDF] L. Shi, D. Keefe, E. Durand, H. Feng, D. Zhang, and J. Lieberman Granzyme B Binds to Target Cells Mostly by Charge and Must Be Added at the Same Time as Perforin to Trigger Apoptosis J. Immunol., May 1, 2005; 174(9): 5456 - 5461. [Abstract] [Full Text] [PDF]

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