Stathmin Regulates Microtubule Dynamics and Microtubule Organizing Center Polarization in Activated T Cells

被引:41
作者
Filbert, Erin L. [1 ]
Le Borgne, Marie [1 ,2 ]
Lin, Joseph [1 ]
Heuser, John E. [3 ]
Shaw, Andrey S. [1 ,2 ]
机构
[1] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA
[3] Washington Univ, Sch Med, Dept Cell Biol, St Louis, MO 63110 USA
基金
美国国家卫生研究院;
关键词
IMMUNOLOGICAL SYNAPSE; PROTEIN-KINASE; CYTOSKELETAL POLARIZATION; CYTOSOLIC TARGET; ANTIGEN RECEPTOR; GOLGI-APPARATUS; PHOSPHORYLATION; PHOSPHOPROTEIN; LYMPHOCYTES; PATHWAYS;
D O I
10.4049/jimmunol.1200242
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Polarization of T cells involves reorientation of the microtubule organizing center (MTOC). Because activated ERK is localized at the immunological synapse, we investigated its role by showing that ERK activation is important for MTOC polarization. Suspecting that ERK phosphorylates a regulator of microtubules, we next focused on stathmin, a known ERK substrate. Our work indicates that during T cell activation, ERK is recruited to the synapse, allowing it to phosphorylate stathmin molecules near the immunological synapse. Supporting an important role of stathmin phosphorylation in T cell activation, we showed that T cell activation results in increased microtubule growth rate dependent on the presence of stathmin. The significance of this finding was demonstrated by results showing that CTLs from stathmin(-/-) mice displayed defective MTOC polarization and defective target cell cytolysis. These data implicate stathmin as a regulator of the microtubule network during T cell activation. The Journal of Immunology, 2012, 188: 5421-5427.
引用
收藏
页码:5421 / 5427
页数:7
相关论文
共 44 条
[1]   A novel microtubule-depolymerizing kinesin involved in length control of a eukaryotic flagellum [J].
Blaineau, Christine ;
Tessier, Magali ;
Dubessay, Pascal ;
Tasse, Lena ;
Crobu, Lucien ;
Pages, Michel ;
Bastien, Patrick .
CURRENT BIOLOGY, 2007, 17 (09) :778-782
[2]  
BROWN DL, 1985, EUR J CELL BIOL, V37, P130
[3]   Quantitative Analysis of ERK2 Interactions with Substrate Proteins ROLES FOR KINASE DOCKING DOMAINS AND ACTIVITY IN DETERMINING BINDING AFFINITY [J].
Burkhard, Kimberly A. ;
Chen, Fengming ;
Shapiro, Paul .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (04) :2477-2485
[4]   CD28-stimulated ERK2 phosphorylation is required for polarization of the microtubule organizing center and granules in YTS NK cells [J].
Chen, Xi ;
Allan, David S. J. ;
Krzewski, Konrad ;
Ge, Baoxue ;
Kopcow, Hernan ;
Strominger, Jack L. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (27) :10346-10351
[5]  
Curmi PA, 1999, CELL STRUCT FUNCT, V24, P345
[6]  
DIANZANI U, 1992, J IMMUNOL, V148, P678
[7]   Phosphorylation regulates the microtubule-destabilizing activity of stathmin and its interaction with tubulin [J].
DiPaolo, G ;
Antonsson, B ;
Kassel, D ;
Riederer, BM ;
Grenningloh, G .
FEBS LETTERS, 1997, 416 (02) :149-152
[8]  
Ebinu JO, 2000, BLOOD, V95, P3199
[9]   The Mitogen-Activated Protein Kinase Scaffold KSR1 Is Required for Recruitment of Extracellular Signal-Regulated Kinase to the Immunological Synapse [J].
Giurisato, Emanuele ;
Lin, Joseph ;
Harding, Angus ;
Cerutti, Elisa ;
Cella, Marina ;
Lewis, Robert E. ;
Colonna, Marco ;
Shaw, Andrey S. .
MOLECULAR AND CELLULAR BIOLOGY, 2009, 29 (06) :1554-1564
[10]   The Immunological Synapse: A Molecular Machine Controlling T Cell Activation [J].
Grakoui, Arash ;
Bromley, Shannon K. ;
Sumen, Cenk ;
Davis, Mark M. ;
Shaw, Andrey S. ;
Allen, Paul M. ;
Dustin, Michael L. .
JOURNAL OF IMMUNOLOGY, 2015, 194 (09) :221-227