Localized diacylglycerol drives the polarization of the microtubule-organizing center in T cells.

作者: Emily J Quann , Ernesto Merino , Toshiaki Furuta , Morgan Huse

DOI: 10.1038/NI.1734

关键词:

摘要: The reorientation of the T cell microtubule-organizing center (MTOC) toward antigen-presenting enables directional secretion cytokines and lytic factors. By single-cell photoactivation antigen receptor, we show that MTOC polarization is driven by localized accumulation diacylglycerol (DAG). was closely preceded first production DAG then recruitment microtubule motor protein dynein. Blocking or disrupting localization impaired recruitment. Localized also required for cytotoxic cell-mediated killing. Furthermore, itself sufficient to induce transient polarization. Our data identify a DAG-dependent pathway signals through dynein control polarity in cells.

参考文章(41)
Lismaida Jusino, Caitlin E. Sedwick, Janis K. Burkhardt, Judy L. Cannon, Jim Miller, Margaret M. Morgan, TCR, LFA-1, and CD28 Play Unique and Complementary Roles in Signaling T Cell Cytoskeletal Reorganization Journal of Immunology. ,vol. 162, pp. 1367- 1375 ,(1999)
G.A. Jones, G Carpenter, The regulation of phospholipase C-gamma 1 by phosphatidic acid. Assessment of kinetic parameters. Journal of Biological Chemistry. ,vol. 268, pp. 20845- 20850 ,(1993) , 10.1016/S0021-9258(19)36862-0
Michelle R. Kuhné, Joseph Lin, Deborah Yablonski, Marianne N. Mollenauer, Lauren I. Richie Ehrlich, Johannes Huppa, Mark M. Davis, Arthur Weiss, Linker for Activation of T Cells, ζ-Associated Protein-70, and Src Homology 2 Domain-Containing Leukocyte Protein-76 are Required for TCR-Induced Microtubule-Organizing Center Polarization Journal of Immunology. ,vol. 171, pp. 860- 866 ,(2003) , 10.4049/JIMMUNOL.171.2.860
Julius O. Ebinu, Stacey L. Stang, Christine Teixeira, Drell A. Bottorff, Jonathan Hooton, Peter M. Blumberg, Michele Barry, R. Chris Bleakley, Hanne L. Ostergaard, James C. Stone, RasGRP links T-cell receptor signaling to Ras. Blood. ,vol. 95, pp. 3199- 3203 ,(2000) , 10.1182/BLOOD.V95.10.3199
Peter Devreotes, Chris Janetopoulos, Eukaryotic chemotaxis: distinctions between directional sensing and polarization. Journal of Biological Chemistry. ,vol. 278, pp. 20445- 20448 ,(2003) , 10.1074/JBC.R300010200
Béatrice Breart, Fabrice Lemaître, Susanna Celli, Philippe Bousso, Two-photon imaging of intratumoral CD8+ T cell cytotoxic activity during adoptive T cell therapy in mice Journal of Clinical Investigation. ,vol. 118, pp. 1390- 1397 ,(2008) , 10.1172/JCI34388
L. Stowers, D. Yelon, L. J. Berg, J. Chant, Regulation of the polarization of T cells toward antigen-presenting cells by Ras-related GTPase CDC42 Proceedings of the National Academy of Sciences of the United States of America. ,vol. 92, pp. 5027- 5031 ,(1995) , 10.1073/PNAS.92.11.5027
Stephen C. Bunnell, Veena Kapoor, Ronald P. Trible, Weiguo Zhang, Lawrence E. Samelson, Dynamic Actin Polymerization Drives T Cell Receptor–Induced Spreading Immunity. ,vol. 14, pp. 315- 329 ,(2001) , 10.1016/S1074-7613(01)00112-1
Connie L. Sommers, Lawrence E. Samelson, Paul E. Love, LAT: a T lymphocyte adapter protein that couples the antigen receptor to downstream signaling pathways. BioEssays. ,vol. 26, pp. 61- 67 ,(2004) , 10.1002/BIES.10384
Jane C. Stinchcombe, Giovanna Bossi, Sarah Booth, Gillian M. Griffiths, The Immunological Synapse of CTL Contains a Secretory Domain and Membrane Bridges Immunity. ,vol. 15, pp. 751- 761 ,(2001) , 10.1016/S1074-7613(01)00234-5