Effects of intracellular calcium and actin cytoskeleton on TCR mobility measured by fluorescence recovery.
BACKGROUND: The activation of T lymphocytes by specific antigen is accompanied by the formation of a specialized signaling region termed the immunological synapse, characterized by the clustering and segregation of surface molecules and, in particular, by T cell receptor (TCR) clustering. METHODOLO...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Public Library of Science
2008
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| _version_ | 1797093502540054528 |
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| author | Dushek, O Mueller, S Soubies, S Depoil, D Caramalho, I Coombs, D Valitutti, S |
| author_facet | Dushek, O Mueller, S Soubies, S Depoil, D Caramalho, I Coombs, D Valitutti, S |
| author_sort | Dushek, O |
| collection | OXFORD |
| description | BACKGROUND: The activation of T lymphocytes by specific antigen is accompanied by the formation of a specialized signaling region termed the immunological synapse, characterized by the clustering and segregation of surface molecules and, in particular, by T cell receptor (TCR) clustering. METHODOLOGY/PRINCIPAL FINDINGS: To better understand TCR motion during cellular activation, we used confocal microscopy and photo-bleaching recovery techniques to investigate the lateral mobility of TCR on the surface of human T lymphocytes under various pharmacological treatments. Using drugs that cause an increase in intracellular calcium, we observed a decrease in TCR mobility that was dependent on a functional actin cytoskeleton. In parallel experiments measurement of filamentous actin by FACS analysis showed that raising intracellular calcium also causes increased polymerization of the actin cytoskeleton. These in vitro results were analyzed using a mathematical model that revealed effective binding parameters between TCR and the actin cytoskeleton. CONCLUSION/SIGNIFICANCE: We propose, based on our results, that increase in intracellular calcium levels leads to actin polymerization and increases TCR/cytoskeleton interactions that reduce the overall mobility of the TCR. In a physiological setting, this may contribute to TCR re-positioning at the immunological synapse. |
| first_indexed | 2024-03-07T04:01:24Z |
| format | Journal article |
| id | oxford-uuid:c4b1b6ff-b5f6-43fd-94ce-9cf8ea0999d0 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:01:24Z |
| publishDate | 2008 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:c4b1b6ff-b5f6-43fd-94ce-9cf8ea0999d02022-03-27T06:25:27ZEffects of intracellular calcium and actin cytoskeleton on TCR mobility measured by fluorescence recovery.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c4b1b6ff-b5f6-43fd-94ce-9cf8ea0999d0EnglishSymplectic Elements at OxfordPublic Library of Science2008Dushek, OMueller, SSoubies, SDepoil, DCaramalho, ICoombs, DValitutti, S BACKGROUND: The activation of T lymphocytes by specific antigen is accompanied by the formation of a specialized signaling region termed the immunological synapse, characterized by the clustering and segregation of surface molecules and, in particular, by T cell receptor (TCR) clustering. METHODOLOGY/PRINCIPAL FINDINGS: To better understand TCR motion during cellular activation, we used confocal microscopy and photo-bleaching recovery techniques to investigate the lateral mobility of TCR on the surface of human T lymphocytes under various pharmacological treatments. Using drugs that cause an increase in intracellular calcium, we observed a decrease in TCR mobility that was dependent on a functional actin cytoskeleton. In parallel experiments measurement of filamentous actin by FACS analysis showed that raising intracellular calcium also causes increased polymerization of the actin cytoskeleton. These in vitro results were analyzed using a mathematical model that revealed effective binding parameters between TCR and the actin cytoskeleton. CONCLUSION/SIGNIFICANCE: We propose, based on our results, that increase in intracellular calcium levels leads to actin polymerization and increases TCR/cytoskeleton interactions that reduce the overall mobility of the TCR. In a physiological setting, this may contribute to TCR re-positioning at the immunological synapse. |
| spellingShingle | Dushek, O Mueller, S Soubies, S Depoil, D Caramalho, I Coombs, D Valitutti, S Effects of intracellular calcium and actin cytoskeleton on TCR mobility measured by fluorescence recovery. |
| title | Effects of intracellular calcium and actin cytoskeleton on TCR mobility measured by fluorescence recovery. |
| title_full | Effects of intracellular calcium and actin cytoskeleton on TCR mobility measured by fluorescence recovery. |
| title_fullStr | Effects of intracellular calcium and actin cytoskeleton on TCR mobility measured by fluorescence recovery. |
| title_full_unstemmed | Effects of intracellular calcium and actin cytoskeleton on TCR mobility measured by fluorescence recovery. |
| title_short | Effects of intracellular calcium and actin cytoskeleton on TCR mobility measured by fluorescence recovery. |
| title_sort | effects of intracellular calcium and actin cytoskeleton on tcr mobility measured by fluorescence recovery |
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