| Sustained LFA-1 cluster formation in the immune synapse requires the combined activities of L-plastin and calmodulin. | |
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MedLine Citation:
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PMID: 20683899 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Formation of immune synapses (IS) between T cells and APC requires multiple rearrangements in the actin cytoskeleton and selective receptor accumulation in supramolecular activation clusters (SMAC). The inner cluster (central SMAC) contains the TCR/CD3 complex. The outer cluster (peripheral SMAC) contains the integrin LFA-1 and Talin. Molecular mechanisms selectively stabilizing receptors in the IS remained largely unknown. Here, we demonstrate that sustained LFA-1 clustering in the IS is a consequence of the combined activities of the actin-bundling protein L-plastin (LPL) and calmodulin. Thus, upon antigen-recognition of T cells, LPL accumulated predominantly in the peripheral SMAC. siRNA-mediated knock-down of LPL led to a failure of LFA-1 and Talin redistribution - however, not TCR/CD3 relocalization - into the IS. As a result of this LPL knock-down, the T-cell/APC interface became smaller over time and T-cell proliferation was inhibited. Importantly, binding of calmodulin to LPL was required for the maintenance of LPL in the IS and consequently inhibition of calmodulin also prevented stable accumulation of LFA-1 and Talin, but not CD3, in the IS. |
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Authors:
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Guido H Wabnitz; Philipp Lohneis; Henning Kirchgessner; Beate Jahraus; Susan Gottwald; Mathias Konstandin; Martin Klemke; Yvonne Samstag |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of immunology Volume: 40 ISSN: 1521-4141 ISO Abbreviation: Eur. J. Immunol. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-02 Completed Date: 2010-11-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1273201 Medline TA: Eur J Immunol Country: Germany |
Other Details:
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Languages: eng Pagination: 2437-49 Citation Subset: IM |
Affiliation:
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Institute for Immunology, Ruprecht-Karls-University, Heidelberg, Germany. guido.wabnitz@immu.uni-heidelberg.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Actins
/
genetics,
immunology,
metabolism* Antigen-Presenting Cells / immunology, metabolism, pathology Binding Sites / genetics Calmodulin / metabolism* Cell Line, Tumor Cell Proliferation Cloning, Molecular Enterotoxins / metabolism Humans Immunological Synapses / genetics, immunology, metabolism* Lymphocyte Function-Associated Antigen-1 / immunology, metabolism Membrane Glycoproteins / genetics, immunology, metabolism* Microfilament Proteins / genetics, immunology, metabolism* Microscopy, Confocal Mutagenesis, Site-Directed Protein Binding / genetics Protein Transport / drug effects, genetics RNA, Small Interfering / genetics Sequence Deletion / genetics Sulfonamides / pharmacology T-Lymphocytes / drug effects, immunology, metabolism*, pathology |
| Chemical | |
Reg. No./Substance:
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0/Actins; 0/Calmodulin; 0/Enterotoxins; 0/Lymphocyte Function-Associated Antigen-1; 0/Membrane Glycoproteins; 0/Microfilament Proteins; 0/RNA, Small Interfering; 0/Sulfonamides; 0/plastin; 39424-53-8/enterotoxin B, staphylococcal; 65595-90-6/W 7 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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