PKCθ regulates T cell motility via ezrin-radixin-moesin localization to the uropod

PLoS One. 2013 Nov 8;8(11):e78940. doi: 10.1371/journal.pone.0078940. eCollection 2013.

Abstract

Cell motility is a fundamental process crucial for function in many cell types, including T cells. T cell motility is critical for T cell-mediated immune responses, including initiation, activation, and effector function. While many extracellular receptors and cytoskeletal regulators have been shown to control T cell migration, relatively few signaling mediators have been identified that can modulate T cell motility. In this study, we find a previously unknown role for PKCθ in regulating T cell migration to lymph nodes. PKCθ localizes to the migrating T cell uropod and regulates localization of the MTOC, CD43 and ERM proteins to the uropod. Furthermore, PKCθ-deficient T cells are less responsive to chemokine induced migration and are defective in migration to lymph nodes. Our results reveal a novel role for PKCθ in regulating T cell migration and demonstrate that PKCθ signals downstream of CCR7 to regulate protein localization and uropod formation.

Publication types

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

MeSH terms

  • Cell Movement / genetics*
  • Cytoskeletal Proteins / metabolism
  • DNA-Binding Proteins / metabolism
  • Humans
  • Immunity, Cellular / genetics*
  • Isoenzymes / genetics*
  • Isoenzymes / metabolism
  • Leukosialin / metabolism
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Membrane Proteins / metabolism
  • Microfilament Proteins / metabolism
  • Microtubule-Organizing Center / metabolism
  • Protein Kinase C / genetics*
  • Protein Kinase C / metabolism
  • Protein Kinase C-theta
  • Receptors, CCR7 / metabolism*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Transcription Factors / metabolism

Substances

  • CCR7 protein, human
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • ETV5 protein, human
  • Isoenzymes
  • Leukosialin
  • Membrane Proteins
  • Microfilament Proteins
  • Receptors, CCR7
  • SPN protein, human
  • Transcription Factors
  • ezrin
  • moesin
  • radixin
  • PRKCQ protein, human
  • Protein Kinase C
  • Protein Kinase C-theta