SEARCH:   Advanced

Blood, 15 May 2004, Vol. 103, No. 10, pp. 3845-3853. Prepublished online as a Blood First Edition Paper on January 22, 2004; DOI 10.1182/blood-2003-06-2156. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-06-2156v1 103/10/3845    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Veugelers, K. Articles by Bleackley, R. C. Search for Related Content PubMed PubMed Citation Articles by Veugelers, K. Articles by Bleackley, R. C. Related Collections Immunobiology Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY The granzyme B–serglycin complex from cytotoxic granules requires dynamin for endocytosis Kirstin Veugelers, Bruce Motyka, Christine Frantz, Irene Shostak, Tracy Sawchuk, and R. Chris Bleackley From the Department of Biochemistry, University of Alberta, Edmonton, AB, Canada. Cytotoxic T lymphocytes and natural killer cells destroy target cells via the directed exocytosis of lytic effector molecules such as perforin and granzymes. The mechanism by which these proteins enter targets is uncertain. There is ongoing debate over whether the most important endocytic mechanism is nonspecific or is dependent on the cation-independent mannose 6-phosphate receptor. This study tested whether granzyme B endocytosis is facilitated by dynamin, a key factor in many endocytic pathways. Uptake of and killing by the purified granzyme B molecule occurred by both dynamin-dependent and -independent mechanisms. However most importantly, serglycin-bound granzyme B in high-molecular-weight degranulate material from cytotoxic T lymphocytes predominantly followed a dynamin-dependent pathway to kill target cells. Similarly, killing by live cytotoxic T lymphocytes was attenuated by a defect in the dynamin endocytic pathway, and in particular, the pathways characteristically activated by granzyme B were affected. We therefore propose a model where degranulated serglycin-bound granzymes require dynamin for uptake. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. A. Kunder, A. L. St. John, G. Li, K. W. Leong, B. Berwin, H. F. Staats, and S. N. Abraham Mast cell-derived particles deliver peripheral signals to remote lymph nodes J. Exp. Med., October 26, 2009; 206(11): 2455 - 2467. [Abstract] [Full Text] [PDF] L. N. Arneson, C. M. Segovis, T. S. Gomez, R. A. Schoon, C. J. Dick, Z. Lou, D. D. Billadeau, and P. J. Leibson Dynamin 2 Regulates Granule Exocytosis during NK Cell-Mediated Cytotoxicity J. Immunol., November 15, 2008; 181(10): 6995 - 7001. [Abstract] [Full Text] [PDF] K. Hallermalm, K. Seki, A. De Geer, B. Motyka, R. C. Bleackley, M. J. Jager, C. J. Froelich, R. Kiessling, V. Levitsky, and J. Levitskaya Modulation of the Tumor Cell Phenotype by IFN-{gamma} Results in Resistance of Uveal Melanoma Cells to Granule-Mediated Lysis by Cytotoxic Lymphocytes J. Immunol., March 15, 2008; 180(6): 3766 - 3774. [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] S. Sipione, C. Ewen, I. Shostak, M. Michalak, and R. C. Bleackley Impaired Cytolytic Activity in Calreticulin-Deficient CTLs J. Immunol., March 15, 2005; 174(6): 3212 - 3219. [Abstract] [Full Text] [PDF] J. C. Choy, V. H.Y. Hung, A. L. Hunter, P. K. Cheung, B. Motyka, I. S. Goping, T. Sawchuk, R. C. Bleackley, T. J. Podor, B. M. McManus, et al. Granzyme B Induces Smooth Muscle Cell Apoptosis in the Absence of Perforin: Involvement of Extracellular Matrix Degradation Arterioscler Thromb Vasc Biol, December 1, 2004; 24(12): 2245 - 2250. [Abstract] [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020