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| Subject Categories: Signal Transduction | Immunology |
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| The EMBO Journal
(2002) 21, 1899–1908, doi: 10.1093/emboj/21.8.1899 |
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| TCR signal initiation machinery is pre-assembled and activated in a subset of membrane rafts |
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| Philippe Drevot1, 5, Claire Langlet1, 5, Xiao-Jun Guo2, Anne-Marie Bernard1, Odile Colard3, Jean-Paul Chauvin4, Rémi Lasserre1 and Hai-Tao He1 |
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1 Centre d'Immunologie de Marseille-Luminy, CNRS-INSERM-Université de la Mediterranee, Case 906, F-13288 Marseille Cedex 9, France 2 LBBN, CNRS-ESA 6033, Faculté des Sciences et Techniques de Saint-Jérôme, F-13397 Marseille Cedex 20, France 3 INSERM U538, CHU Saint-Antoine, 27 rue de Chaligny, F-75012 Paris France 4 LGPD-IBDM, Case 907, F-13288 Marseille Cedex 9, France 5 P.Drevot and C.Langlet contributed equally to this work To whom correspondence should be addressed Hai-Tao He, he@ciml.univ-mrs.fr Received 12 November 2001; Revised 17 January 2002; Accepted 21 February 2002. |
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| Abstract |
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Recent studies suggest that rafts are involved in numerous cell functions, including membrane traffic and signaling. Here we demonstrate, using a polyoxyethylene ether Brij 98, that detergent-insoluble microdomains possessing the expected biochemical characteristics of rafts are present in the cell membrane at 37°C. After extraction, these microdomains are visualized as membrane vesicles with a mean diameter of  70 nm. These findings provide further evidence for the existence of rafts under physiological conditions and are the basis of a new isolation method allowing more accurate analyses of raft structure. We found that main components of T cell receptor (TCR) signal initiation machinery, i.e. TCR−CD3 complex, Lck and ZAP-70 kinases, and CD4 co-receptor are constitutively partitioned into a subset of rafts. Functional studies in both intact cells and isolated rafts showed that upon ligation, TCR initiates the signaling in this specialized raft subset. Our data thus strongly indicate an important role of rafts in organizing TCR early signaling pathways within small membrane microdomains, both prior to and following receptor engagement, for efficient TCR signal initiation upon stimulation. |
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| Keywords: lipid raft, membrane domain, signal transduction, T cell receptor |
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