Cutting Edge: Localization of Linker for Activation of T Cells to Lipid Rafts Is Not Essential in T Cell Activation and Development

作者: Minghua Zhu , Shudan Shen , Yan Liu , Olivia Granillo , Weiguo Zhang

DOI: 10.4049/JIMMUNOL.174.1.31

关键词:

摘要: It has been proposed that upon T cell activation, linker for activation of cells (LAT), a transmembrane adaptor protein localized to lipid rafts, orchestrates formation multiprotein complexes and activates signaling cascades in rafts. However, whether rafts really exist or function remains controversial. To address the importance LAT function, we generated fusion target nonraft fractions using domain from protein, X (LAX). Surprisingly, this functioned well TCR signaling. restored MAPK calcium flux, NFAT LAT-deficient cells. further study vivo, transgenic mice express protein. Analysis these indicated it was fully capable replacing thymocyte development function. Our results demonstrate localization is not essential during normal development.

参考文章(16)
Sean Munro, Lipid Rafts: Elusive or Illusive? Cell. ,vol. 115, pp. 377- 388 ,(2003) , 10.1016/S0092-8674(03)00882-1
Weiguo Zhang, Joanne Sloan-Lancaster, Jason Kitchen, Ronald P Trible, Lawrence E Samelson, LAT Cell. ,vol. 92, pp. 83- 92 ,(1998) , 10.1016/S0092-8674(00)80901-0
Bodil Ramstedt, J.Peter Slotte, Membrane properties of sphingomyelins FEBS Letters. ,vol. 531, pp. 33- 37 ,(2002) , 10.1016/S0014-5793(02)03406-3
P E Love, E W Shores, E J Lee, A Grinberg, T I Munitz, H Westphal, A Singer, Differential effects of zeta and eta transgenes on early alpha/beta T cell development. Journal of Experimental Medicine. ,vol. 179, pp. 1485- 1494 ,(1994) , 10.1084/JEM.179.5.1485
Timothy S Finco, Theresa Kadlecek, Weiguo Zhang, Lawrence E Samelson, Arthur Weiss, LAT Is Required for TCR-Mediated Activation of PLCγ1 and the Ras Pathway Immunity. ,vol. 9, pp. 617- 626 ,(1998) , 10.1016/S1074-7613(00)80659-7
Paola Pizzo, Emanuele Giurisato, Maristella Tassi, Angelo Benedetti, Tullio Pozzan, Antonella Viola, Lipid rafts and T cell receptor signaling: a critical re-evaluation. European Journal of Immunology. ,vol. 32, pp. 3082- 3091 ,(2002) , 10.1002/1521-4141(200211)32:11<3082::AID-IMMU3082>3.0.CO;2-2
Minghua Zhu, Erin Janssen, Kin Leung, Weiguo Zhang, Molecular cloning of a novel gene encoding a membrane-associated adaptor protein (LAX) in lymphocyte signaling. Journal of Biological Chemistry. ,vol. 277, pp. 46151- 46158 ,(2002) , 10.1074/JBC.M208946200
Deborah A. Brown, Erwin London, Structure and Function of Sphingolipid- and Cholesterol-rich Membrane Rafts Journal of Biological Chemistry. ,vol. 275, pp. 17221- 17224 ,(2000) , 10.1074/JBC.R000005200
Christine Montixi, Claire Langlet, Anne-Marie Bernard, Jean Thimonier, Catherine Dubois, Marc-André Wurbel, Jean-Paul Chauvin, Michel Pierres, Hai-Tao He, Engagement of T cell receptor triggers its recruitment to low-density detergent-insoluble membrane domains The EMBO Journal. ,vol. 17, pp. 5334- 5348 ,(1998) , 10.1093/EMBOJ/17.18.5334