Stathmin regulates microtubule dynamics and microtubule organizing center polarization in activated T cells

J Immunol. 2012 Jun 1;188(11):5421-7. doi: 10.4049/jimmunol.1200242. Epub 2012 Apr 23.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Enlargement
  • Cell Polarity / immunology*
  • Cells, Cultured
  • Humans
  • Jurkat Cells
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Microtubule-Organizing Center / immunology
  • Microtubule-Organizing Center / metabolism*
  • Phosphorylation / immunology
  • Stathmin / deficiency
  • Stathmin / metabolism
  • Stathmin / physiology*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*

Substances

  • Stathmin
  • Stmn1 protein, mouse