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

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...

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Main Authors: Liu, D, Bryceson, Y, Meckel, T, Vasiliver-Shamis, G, Dustin, M, Long, E
Format: Journal article
Language:English
Published: 2009
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author Liu, D
Bryceson, Y
Meckel, T
Vasiliver-Shamis, G
Dustin, M
Long, E
author_facet Liu, D
Bryceson, Y
Meckel, T
Vasiliver-Shamis, G
Dustin, M
Long, E
author_sort Liu, D
collection OXFORD
description 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.
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spelling oxford-uuid:85c010ef-f7c6-4243-a9bc-35fa5176f5d92022-03-26T21:59:33ZIntegrin-dependent organization and bidirectional vesicular traffic at cytotoxic immune synapses.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:85c010ef-f7c6-4243-a9bc-35fa5176f5d9EnglishSymplectic Elements at Oxford2009Liu, DBryceson, YMeckel, TVasiliver-Shamis, GDustin, MLong, ECytotoxic 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.
spellingShingle Liu, D
Bryceson, Y
Meckel, T
Vasiliver-Shamis, G
Dustin, M
Long, E
Integrin-dependent organization and bidirectional vesicular traffic at cytotoxic immune synapses.
title Integrin-dependent organization and bidirectional vesicular traffic at cytotoxic immune synapses.
title_full Integrin-dependent organization and bidirectional vesicular traffic at cytotoxic immune synapses.
title_fullStr Integrin-dependent organization and bidirectional vesicular traffic at cytotoxic immune synapses.
title_full_unstemmed Integrin-dependent organization and bidirectional vesicular traffic at cytotoxic immune synapses.
title_short Integrin-dependent organization and bidirectional vesicular traffic at cytotoxic immune synapses.
title_sort integrin dependent organization and bidirectional vesicular traffic at cytotoxic immune synapses
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AT meckelt integrindependentorganizationandbidirectionalvesiculartrafficatcytotoxicimmunesynapses
AT vasilivershamisg integrindependentorganizationandbidirectionalvesiculartrafficatcytotoxicimmunesynapses
AT dustinm integrindependentorganizationandbidirectionalvesiculartrafficatcytotoxicimmunesynapses
AT longe integrindependentorganizationandbidirectionalvesiculartrafficatcytotoxicimmunesynapses