TAGLN2 regulates T cell activation by stabilizing the actin cytoskeleton at the immunological synapse

J Cell Biol. 2015 Apr 13;209(1):143-62. doi: 10.1083/jcb.201407130.

Abstract

The formation of an immunological synapse (IS) requires tight regulation of actin dynamics by many actin polymerizing/depolymerizing proteins. However, the significance of actin stabilization at the IS remains largely unknown. In this paper, we identify a novel function of TAGLN2--an actin-binding protein predominantly expressed in T cells--in stabilizing cortical F-actin, thereby maintaining F-actin contents at the IS and acquiring LFA-1 (leukocyte function-associated antigen-1) activation after T cell receptor stimulation. TAGLN2 blocks actin depolymerization and competes with cofilin both in vitro and in vivo. Knockout of TAGLN2 (TAGLN2(-/-)) reduced F-actin content and destabilized F-actin ring formation, resulting in decreased cell adhesion and spreading. TAGLN2(-/-) T cells displayed weakened cytokine production and cytotoxic effector function. These findings reveal a novel function of TAGLN2 in enhancing T cell responses by controlling actin stability at the IS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism*
  • Actin Depolymerizing Factors / metabolism
  • Animals
  • Binding, Competitive
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Humans
  • Immunological Synapses / metabolism*
  • Immunological Synapses / ultrastructure
  • Jurkat Cells
  • Lymphocyte Activation
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microfilament Proteins / physiology*
  • Muscle Proteins / physiology*
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Stability

Substances

  • Actin Depolymerizing Factors
  • Microfilament Proteins
  • Muscle Proteins
  • Tagln2 protein, mouse