Casein kinase I delta controls centrosome positioning during T cell activation

J Cell Biol. 2011 Nov 28;195(5):781-97. doi: 10.1083/jcb.201106025.

Abstract

Although termed central body, the centrosome is located off-center in many polarized cells. T cell receptor (TCR) engagement by antigens induces a polarity switch in T cells. This leads to the recruitment of the centrosome to the immunological synapse (IS), a specialized cell-cell junction. Despite much recent progress, how TCR signaling triggers centrosome repositioning remains poorly understood. In this paper, we uncover a critical requirement for the centrosomal casein kinase I delta (CKIδ) in centrosome translocation to the IS. CKIδ binds and phosphorylates the microtubule plus-end-binding protein EB1. Moreover, a putative EB1-binding motif at the C terminus of CKIδ is required for centrosome translocation to the IS. We find that depletion of CKIδ in T lymphocytes and inhibition of CKI in epithelial cells reduce microtubule growth. Therefore, we propose that CKIδ-EB1 complexes contribute to the increase in microtubule growth speeds observed in polarized T cells, a mechanism that might serve to generate long-stable microtubules necessary for centrosome translocation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Benzamides / pharmacology
  • Biological Transport
  • Casein Kinase Idelta / antagonists & inhibitors
  • Casein Kinase Idelta / genetics
  • Casein Kinase Idelta / metabolism
  • Casein Kinase Idelta / physiology*
  • Cell Line
  • Cell Polarity
  • Centrosome / metabolism*
  • Humans
  • Imidazoles / pharmacology
  • Jurkat Cells
  • Lymphocyte Activation
  • Microtubule-Associated Proteins
  • Microtubules / metabolism
  • Phosphorylation
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / physiology
  • T-Lymphocytes / ultrastructure

Substances

  • 4-(4-(2,3-dihydrobenzo(1,4)dioxin-6-yl)-5-pyridin-2-yl-1H-imidazol-2-yl)benzamide
  • Benzamides
  • Imidazoles
  • MAPRE1 protein, human
  • Microtubule-Associated Proteins
  • Casein Kinase Idelta