ZFIN ID: ZDB-PUB-201021-18
Partial loss of actin nucleator actin-related protein 2/3 activity triggers blebbing in primary T lymphocytes
Obeidy, P., Ju, L.A., Oehlers, S.H., Zulkhernain, N.S., Lee, Q., Galeano Niño, J.L., Kwan, R.Y., Tikoo, S., Cavanagh, L.L., Mrass, P., Cook, A.J., Jackson, S.P., Biro, M., Roediger, B., Sixt, M., Weninger, W.
Date: 2020
Source: Immunology and cell biology   98: 93-113 (Journal)
Registered Authors: Oehlers, Stefan
Keywords: Arp2/3, actin cytoskeleton, blebbing motility, cellular morphology, primary CD8+ T cell
MeSH Terms:
  • Actin Cytoskeleton/metabolism*
  • Actin-Related Protein 2-3 Complex/genetics
  • Actin-Related Protein 2-3 Complex/metabolism*
  • Actin-Related Protein 3/genetics
  • Actin-Related Protein 3/metabolism*
  • Actins/metabolism
  • Animals
  • Cell Line, Tumor
  • Cell Movement/genetics*
  • Cell Proliferation/genetics
  • Cell Survival/genetics
  • Down-Regulation
  • Gene Knockdown Techniques
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • RNA, Small Interfering
  • Single-Cell Analysis
  • T-Lymphocytes, Cytotoxic/cytology
  • T-Lymphocytes, Cytotoxic/metabolism*
  • Zebrafish
PubMed: 31698518 Full text @ Immunol. Cell Biol.
ABSTRACT
T lymphocytes utilize amoeboid migration to navigate effectively within complex microenvironments. The precise rearrangement of the actin cytoskeleton required for cellular forward propulsion is mediated by actin regulators, including the actin-related protein 2/3 (Arp2/3) complex, a macromolecular machine that nucleates branched actin filaments at the leading edge. The consequences of modulating Arp2/3 activity on the biophysical properties of the actomyosin cortex and downstream T cell function are incompletely understood. We report that even a moderate decrease of Arp3 levels in T cells profoundly affects actin cortex integrity. Reduction in total F-actin content leads to reduced cortical tension and disrupted lamellipodia formation. Instead, in Arp3-knockdown cells, the motility mode is dominated by blebbing migration characterized by transient, balloon-like protrusions at the leading edge. Although this migration mode seems to be compatible with interstitial migration in three-dimensional environments, diminished locomotion kinetics and impaired cytotoxicity interfere with optimal T cell function. These findings define the importance of finely tuned, Arp2/3-dependent mechanophysical membrane integrity in cytotoxic effector T lymphocyte activities.
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