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Intercellular Transfer of Oncogenic H-Ras at the Immunological Synapse
Immune cells establish dynamic adhesive cell–cell interactions at a specific contact region, termed the immunological synapse (IS). Intriguing features of the IS are the formation of regions of plasma membrane fusion and the intercellular exchange of membrane fragments between the conjugated cells....
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2065899/ https://www.ncbi.nlm.nih.gov/pubmed/18030338 http://dx.doi.org/10.1371/journal.pone.0001204 |
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author | Rechavi, Oded Goldstein, Itamar Vernitsky, Helly Rotblat, Barak Kloog, Yoel |
author_facet | Rechavi, Oded Goldstein, Itamar Vernitsky, Helly Rotblat, Barak Kloog, Yoel |
author_sort | Rechavi, Oded |
collection | PubMed |
description | Immune cells establish dynamic adhesive cell–cell interactions at a specific contact region, termed the immunological synapse (IS). Intriguing features of the IS are the formation of regions of plasma membrane fusion and the intercellular exchange of membrane fragments between the conjugated cells. It is not known whether upon IS formation, intact intracellular proteins can transfer from target cells to lymphocytes to allow the transmission of signals across cell boundaries. Here we show by both FACS and confocal microscopy that human lymphocytes acquire from the cells they scan the inner-membrane protein H-Ras, a G-protein vital for common lymphocyte functions and a prominent participant in human cancer. The transfer was cell contact-dependent and occurred in the context of cell-conjugate formation. Moreover, the acquisition of oncogenic H-RasG12V by natural killer (NK) and T lymphocytes had important biological functions in the adopting lymphocytes: the transferred H-RasG12V induced ERK phosphorylation, increased interferon-γ and tumor necrosis factor-α secretion, enhanced lymphocyte proliferation, and augmented NK-mediated target cell killing. Our findings reveal a novel mode of cell-to-cell communication—allowing lymphocytes to extend the confines of their own proteome—which may moreover play an important role in natural tumor immunity. |
format | Text |
id | pubmed-2065899 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-20658992007-11-21 Intercellular Transfer of Oncogenic H-Ras at the Immunological Synapse Rechavi, Oded Goldstein, Itamar Vernitsky, Helly Rotblat, Barak Kloog, Yoel PLoS One Research Article Immune cells establish dynamic adhesive cell–cell interactions at a specific contact region, termed the immunological synapse (IS). Intriguing features of the IS are the formation of regions of plasma membrane fusion and the intercellular exchange of membrane fragments between the conjugated cells. It is not known whether upon IS formation, intact intracellular proteins can transfer from target cells to lymphocytes to allow the transmission of signals across cell boundaries. Here we show by both FACS and confocal microscopy that human lymphocytes acquire from the cells they scan the inner-membrane protein H-Ras, a G-protein vital for common lymphocyte functions and a prominent participant in human cancer. The transfer was cell contact-dependent and occurred in the context of cell-conjugate formation. Moreover, the acquisition of oncogenic H-RasG12V by natural killer (NK) and T lymphocytes had important biological functions in the adopting lymphocytes: the transferred H-RasG12V induced ERK phosphorylation, increased interferon-γ and tumor necrosis factor-α secretion, enhanced lymphocyte proliferation, and augmented NK-mediated target cell killing. Our findings reveal a novel mode of cell-to-cell communication—allowing lymphocytes to extend the confines of their own proteome—which may moreover play an important role in natural tumor immunity. Public Library of Science 2007-11-21 /pmc/articles/PMC2065899/ /pubmed/18030338 http://dx.doi.org/10.1371/journal.pone.0001204 Text en Rechavi et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Rechavi, Oded Goldstein, Itamar Vernitsky, Helly Rotblat, Barak Kloog, Yoel Intercellular Transfer of Oncogenic H-Ras at the Immunological Synapse |
title | Intercellular Transfer of Oncogenic H-Ras at the Immunological Synapse |
title_full | Intercellular Transfer of Oncogenic H-Ras at the Immunological Synapse |
title_fullStr | Intercellular Transfer of Oncogenic H-Ras at the Immunological Synapse |
title_full_unstemmed | Intercellular Transfer of Oncogenic H-Ras at the Immunological Synapse |
title_short | Intercellular Transfer of Oncogenic H-Ras at the Immunological Synapse |
title_sort | intercellular transfer of oncogenic h-ras at the immunological synapse |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2065899/ https://www.ncbi.nlm.nih.gov/pubmed/18030338 http://dx.doi.org/10.1371/journal.pone.0001204 |
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