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Visualizing the Actin and Microtubule Cytoskeletons at the B-cell Immune Synapse Using Stimulated Emission Depletion (STED) Microscopy
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Visualizing the Actin and Microtubule Cytoskeletons at the B-cell Immune Synapse Using Stimulated Emission Depletion (STED) Microscopy

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NK cell lytic granules are highly motile at the immunological synapse and require F-actin for post-degranulation

Emily M Mace1, Winona W Wu, Tina Ho

  • 1Baylor College of Medicine, Houston, TX 77030, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|October 16, 2012
PubMed

Insights

Cytolytic granules in natural killer (NK) cells move dynamically within the immunological synapse (IS) before releasing their toxic contents. Granule persistence after degranulation relies on the actin network integrity at the IS.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Natural killer (NK) cells are crucial for cytotoxic immunity.
  • Formation of the immunological synapse (IS) and polarization of cytolytic granules are key to NK cell function.
  • Lytic granules must navigate the actin network at the IS to deliver cytotoxic contents.

Purpose of the Study:

  • To investigate the motility and persistence of lytic granules at the cell cortex of activated human NK cells.
  • To understand the role of the actin cytoskeleton in lytic granule dynamics during NK cell-mediated cytotoxicity.

Main Methods:

  • Utilized high-resolution total internal reflection fluorescence microscopy.
  • Employed highly quantitative analysis techniques to track lytic granule movement.
  • Assessed the impact of actin depolymerization using Latrunculin A.

Main Results:

  • Lytic granules exhibit significant motility at the cell cortex before degranulation.
  • Granule motility was not significantly altered by Latrunculin A after polarization.
  • Lytic granule persistence at the cortex significantly decreased after degranulation.
  • Synaptic actin network integrity is required for post-exocytosis granule persistence.

Conclusions:

  • Lytic granules are highly dynamic within the human NK cell IS prior to degranulation.
  • The actin network at the IS is essential for maintaining granule persistence after exocytosis.
  • These findings elucidate the mechanics of cytotoxic granule release in NK cells.

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