T lymphocyte myosin IIA is required for maturation of the immunological synapse

Sudha Kumari, Santosha Vardhana, Michael Cammer, Silvia Curado, Luis Santos, Michael Sheetz, Michael L. Dustin

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

The role of non-muscle myosin IIA (heavy chain encoded by the non-muscle myosin heavy chain 9 gene, Myh9) in immunological synapse formation is controversial. We have addressed the role ofmyosin IIA heavy chain protein (MYH9) in mouseT cells responding to MHC-peptide complexes and ICAM-1 in supported planar bilayers - a model for immunological synapse maturation. We found that reduction of MYH9 expression levels using Myh9 siRNA in proliferating mouse CD4+ AND T cell receptor (TCR) transgenic T cells resulted in increased spreading area, failure to assemble the central and peripheral supramolecular activation clusters (cSMAC and pSMAC), and increased motility. Surprisingly, TCR microcluster speed was reduced marginally, however TCR microclusters dissipated prior to forming a cSMAC. TCR microclusters formed in the Myh9 siRNA-treatedT cells showed reduced phosphorylation of the Src family kinase (SFK) activation loop and displayed reduced cytoplasmic calcium ion (Ca2+) elevation. In addition, Myh9 siRNA-treated cells displayed reduced phosphorylation of the Cas-L substrate domain - a force-dependent SFK substrate - which was observed in control siRNA-treated cells in foci throughout the immunological synapse except the cSMAC. Cas-L exhibited TCR ligation-dependent induction of phosphorylation. These results provide further evidence that T cell activation is modulated by intrinsic force-generating systems and can be viewed as a mechanically responsive process influenced by MYH9.

Original languageEnglish (US)
Article numberArticle 230
JournalFrontiers in immunology
Volume3
Issue numberAUG
DOIs
StatePublished - Dec 1 2012
Externally publishedYes

Fingerprint

Nonmuscle Myosin Type IIA
Immunological Synapses
T-Cell Antigen Receptor
Small Interfering RNA
T-Lymphocytes
src-Family Kinases
Myosin Heavy Chains
Phosphorylation
Intercellular Adhesion Molecule-1
Ligation
Ions
Calcium
Peptides
Genes
Proteins

Keywords

  • Antigen
  • Calcium
  • Cytoskeleton
  • Phosphorylation
  • Receptors
  • Signaling
  • Synapse

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Kumari, S., Vardhana, S., Cammer, M., Curado, S., Santos, L., Sheetz, M., & Dustin, M. L. (2012). T lymphocyte myosin IIA is required for maturation of the immunological synapse. Frontiers in immunology, 3(AUG), [Article 230]. https://doi.org/10.3389/fimmu.2012.00230

T lymphocyte myosin IIA is required for maturation of the immunological synapse. / Kumari, Sudha; Vardhana, Santosha; Cammer, Michael; Curado, Silvia; Santos, Luis; Sheetz, Michael; Dustin, Michael L.

In: Frontiers in immunology, Vol. 3, No. AUG, Article 230, 01.12.2012.

Research output: Contribution to journalArticle

Kumari, S, Vardhana, S, Cammer, M, Curado, S, Santos, L, Sheetz, M & Dustin, ML 2012, 'T lymphocyte myosin IIA is required for maturation of the immunological synapse', Frontiers in immunology, vol. 3, no. AUG, Article 230. https://doi.org/10.3389/fimmu.2012.00230
Kumari, Sudha ; Vardhana, Santosha ; Cammer, Michael ; Curado, Silvia ; Santos, Luis ; Sheetz, Michael ; Dustin, Michael L. / T lymphocyte myosin IIA is required for maturation of the immunological synapse. In: Frontiers in immunology. 2012 ; Vol. 3, No. AUG.
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