SEARCH:   Advanced

Blood, 30 July 2009, Vol. 114, No. 5, pp. 1016-1025. Prepublished online as a Blood First Edition Paper on June 3, 2009; DOI 10.1182/blood-2008-03-136770. This Article Full Text Full Text (PDF) Supplemental Methods, Tables, and Figures All Versions of this Article: blood-2008-03-136770v1 114/5/1016    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Nejmeddine, M. Articles by Bangham, C. R. M. PubMed PubMed Citation Articles by Nejmeddine, M. Articles by Bangham, C. R. M. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY HTLV-1–Tax and ICAM-1 act on T-cell signal pathways to polarize the microtubule-organizing center at the virological synapse Mohamed Nejmeddine1, Veera S. Negi2, Sohini Mukherjee2, Yuetsu Tanaka3, Kim Orth2, Graham P. Taylor4, and Charles R. M. Bangham1 1 Department of Immunology, Wright-Fleming Institute, Imperial College, London, United Kingdom; 2 Department of Molecular Biology, University of Texas Southwestern Medical Centre, Dallas; 3 Department of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus, Okinawa, Japan; and 4 Department of Genitourinary Medicine and Communicable Diseases, Wright-Fleming Institute, Imperial College, London, United Kingdom Human T-lymphotropic virus type 1 (HTLV-1) spreads directly between lymphocytes and other cells via a specialized cell-cell contact, termed the virological synapse. The formation of the virological synapse is accompanied by the orientation of the microtubule-organizing center (MTOC) in the infected T cell toward the cell contact region with the noninfected target cell. We previously demonstrated that the combination of intracellular Tax protein expression and the stimulation of the intercellular adhesion molecule-1 (ICAM-1) on the cell surface is sufficient to trigger MTOC polarization in the HTLV-1–infected T cell. However, the mechanism by which Tax and ICAM-1 cause the MTOC polarization is not fully understood. Here we show that the presence of Tax at the MTOC region and its ability to stimulate cyclic AMP-binding protein–dependent pathways are both required for MTOC polarization in the HTLV-1–infected T cell at the virological synapse. Furthermore, we show that the MTOC polarization induced by ICAM-1 engagement depends on activation of the Ras-MEK-ERK signaling pathway. Our findings indicate that efficient MTOC polarization at the virological synapse requires Tax-mediated stimulation of T-cell activation pathways in synergy with ICAM-1 cross-linking. The results also reveal differences in the signaling pathways used to trigger MTOC polarization between the immunologic synapse and the virological synapse. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. M. Taylor, M. Brown, M. Nejmeddine, K. J. Kim, L. Ratner, M. Lairmore, and C. Nicot Novel Role for Interleukin-2 Receptor-Jak Signaling in Retrovirus Transmission J. Virol., November 15, 2009; 83(22): 11467 - 11476. [Abstract] [Full Text] [PDF]

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020