End-binding protein 1 controls signal propagation from the T cell receptor

EMBO J. 2012 Nov 5;31(21):4140-52. doi: 10.1038/emboj.2012.242. Epub 2012 Aug 24.

Abstract

The role of microtubules (MTs) in the control and dynamics of the immune synapse (IS) remains unresolved. Here, we show that T cell activation requires the growth of MTs mediated by the plus-end specific protein end-binding 1 (EB1). A direct interaction of the T cell receptor (TCR) complex with EB1 provides the molecular basis for EB1 activity promoting TCR encounter with signalling vesicles at the IS. EB1 knockdown alters TCR dynamics at the IS and prevents propagation of the TCR activation signal to LAT, thus inhibiting activation of PLCγ1 and its localization to the IS. These results identify a role for EB1 interaction with the TCR in controlling TCR sorting and its connection with the LAT/PLCγ1 signalosome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Blotting, Western
  • Fluorescent Antibody Technique
  • Humans
  • Immunoprecipitation
  • Jurkat Cells
  • Lymphocyte Activation
  • Membrane Proteins / metabolism*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism*
  • Molecular Sequence Data
  • Phospholipase C gamma / metabolism*
  • Phosphorylation
  • Protein Binding
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction*
  • T-Lymphocytes / metabolism
  • Time-Lapse Imaging
  • Two-Hybrid System Techniques
  • Tyrosine / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • LAT protein, human
  • MAPRE1 protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins
  • Tyrosine
  • Phospholipase C gamma