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Integrin-dependent organization and bidirectional vesicular traffic at cytotoxic immune synapses.

Liu, Dongfang and Bryceson, Yenan T. and Meckel, Tobias and Vasiliver-Shamis, Gaia and Dustin, Michael L. and Long, Eric O. (2009):
Integrin-dependent organization and bidirectional vesicular traffic at cytotoxic immune synapses.
In: Immunity, 31 (1), pp. 99-109. ISSN 1097-4180,
[Article]

Abstract

Cytotoxic lymphocytes kill target cells by releasing the content of secretory lysosomes at the immune synapse. To understand the dynamics and control of cytotoxic immune synapses, we imaged human primary, live natural killer cells on lipid bilayers carrying ligands of activation receptors. Formation of an organized synapse was dependent on the presence of the beta2 integrin ligand ICAM-1. Ligands of coactivation receptors 2B4 and NKG2D segregated into central and peripheral regions, respectively. Lysosomal protein LAMP-1 that was exocytosed during degranulation accumulated in a large and spatially stable cluster, which overlapped with a site of membrane internalization. Lysosomal compartments reached the plasma membrane at focal points adjacent to centrally accumulated LAMP-1. Imaging of fixed cells revealed that perforin-containing granules were juxtaposed to an intracellular compartment where exocytosed LAMP-1 was retrieved. Thus, cytotoxic immune synapses include a central region of bidirectional vesicular traffic, which is controlled by integrin signaling.

Item Type: Article
Erschienen: 2009
Creators: Liu, Dongfang and Bryceson, Yenan T. and Meckel, Tobias and Vasiliver-Shamis, Gaia and Dustin, Michael L. and Long, Eric O.
Title: Integrin-dependent organization and bidirectional vesicular traffic at cytotoxic immune synapses.
Language: English
Abstract:

Cytotoxic lymphocytes kill target cells by releasing the content of secretory lysosomes at the immune synapse. To understand the dynamics and control of cytotoxic immune synapses, we imaged human primary, live natural killer cells on lipid bilayers carrying ligands of activation receptors. Formation of an organized synapse was dependent on the presence of the beta2 integrin ligand ICAM-1. Ligands of coactivation receptors 2B4 and NKG2D segregated into central and peripheral regions, respectively. Lysosomal protein LAMP-1 that was exocytosed during degranulation accumulated in a large and spatially stable cluster, which overlapped with a site of membrane internalization. Lysosomal compartments reached the plasma membrane at focal points adjacent to centrally accumulated LAMP-1. Imaging of fixed cells revealed that perforin-containing granules were juxtaposed to an intracellular compartment where exocytosed LAMP-1 was retrieved. Thus, cytotoxic immune synapses include a central region of bidirectional vesicular traffic, which is controlled by integrin signaling.

Journal or Publication Title: Immunity
Journal volume: 31
Number: 1
Divisions: 10 Department of Biology
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10 Department of Biology > Plant Membrane Biophysics
10 Department of Biology > Membrane Dynamics
Date Deposited: 06 Jun 2011 13:34
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