A cascade of protein kinase C isozymes promotes cytoskeletal polarization in T cells

Nat Immunol. 2011 May 22;12(7):647-54. doi: 10.1038/ni.2033.

Abstract

Polarization of the T cell microtubule-organizing center (MTOC) toward the antigen-presenting cell (APC) is driven by the accumulation of diacylglycerol (DAG) at the immunological synapse (IS). The mechanisms that couple DAG to the MTOC are not known. By single-cell photoactivation of the T cell antigen receptor (TCR), we found that three distinct isoforms of protein kinase C (PKC) were recruited by DAG to the IS in two steps. PKC-ɛ and PKC-η accumulated first in a broad region of membrane, whereas PKC-θ arrived later in a smaller zone. Functional experiments indicated that PKC-θ was required for MTOC reorientation and that PKC-ɛ and PKC-η operated redundantly to promote the recruitment of PKC-θ and subsequent polarization responses. Our results establish a previously uncharacterized role for PKC proteins in T cell polarity.

Publication types

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

MeSH terms

  • Animals
  • Antigen-Presenting Cells / cytology
  • Antigen-Presenting Cells / enzymology
  • Antigen-Presenting Cells / immunology
  • Cell Polarity / immunology*
  • Cytoskeleton / enzymology*
  • Cytoskeleton / immunology
  • Diglycerides / immunology
  • Immunological Synapses / enzymology
  • Immunological Synapses / immunology
  • Isoenzymes / immunology*
  • Mice
  • Mice, Transgenic
  • Protein Kinase C / immunology*
  • Protein Kinase C-epsilon / immunology*
  • Protein Kinase C-theta
  • Receptors, Antigen, T-Cell / immunology
  • Single-Cell Analysis
  • T-Lymphocytes / cytology
  • T-Lymphocytes / enzymology*
  • T-Lymphocytes / immunology

Substances

  • Diglycerides
  • Isoenzymes
  • Receptors, Antigen, T-Cell
  • protein kinase C eta
  • Prkcq protein, mouse
  • Protein Kinase C
  • Protein Kinase C-epsilon
  • Protein Kinase C-theta