|
|
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.
 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:
|
|
|
|
 
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]
|
|
|
|
|
