Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2010-9-2
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1521-4141
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2437-49
pubmed:meshHeading
pubmed-meshheading:20683899-Actins, pubmed-meshheading:20683899-Antigen-Presenting Cells, pubmed-meshheading:20683899-Binding Sites, pubmed-meshheading:20683899-Calmodulin, pubmed-meshheading:20683899-Cell Line, Tumor, pubmed-meshheading:20683899-Cell Proliferation, pubmed-meshheading:20683899-Cloning, Molecular, pubmed-meshheading:20683899-Enterotoxins, pubmed-meshheading:20683899-Humans, pubmed-meshheading:20683899-Immunological Synapses, pubmed-meshheading:20683899-Lymphocyte Function-Associated Antigen-1, pubmed-meshheading:20683899-Membrane Glycoproteins, pubmed-meshheading:20683899-Microfilament Proteins, pubmed-meshheading:20683899-Microscopy, Confocal, pubmed-meshheading:20683899-Mutagenesis, Site-Directed, pubmed-meshheading:20683899-Protein Binding, pubmed-meshheading:20683899-Protein Transport, pubmed-meshheading:20683899-RNA, Small Interfering, pubmed-meshheading:20683899-Sequence Deletion, pubmed-meshheading:20683899-Sulfonamides, pubmed-meshheading:20683899-T-Lymphocytes
pubmed:year
2010
pubmed:articleTitle
Sustained LFA-1 cluster formation in the immune synapse requires the combined activities of L-plastin and calmodulin.
pubmed:affiliation
Institute for Immunology, Ruprecht-Karls-University, Heidelberg, Germany. guido.wabnitz@immu.uni-heidelberg.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't