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Rapid lytic granule convergence to the MTOC in natural killer cells is dependent on dynein but not cytolytic

Ashley N Mentlik1, Keri B Sanborn, Erika L Holzbaur

  • 1Department of Pediatrics and Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Molecular Biology of the Cell
|May 7, 2010
PubMed

Insights

Natural killer cells rapidly transport lytic granules to the microtubule-organizing center (MTOC) before MTOC polarization. This dynein-dependent process prepares cells for directed secretion without committing them to cytotoxicity.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Natural killer (NK) cells are crucial for innate immunity, mediating target cell lysis via secretory lysosomes (lytic granules).
  • Directed secretion by NK cells involves forming an immunological synapse and requires sequential actin reorganization followed by microtubule-organizing center (MTOC) polarization.

Purpose of the Study:

  • To elucidate the interrelationship between lytic granule polarization and MTOC polarization during NK cell-mediated cytotoxicity.
  • To define the molecular mechanisms and timing governing lytic granule transport to the MTOC.

Main Methods:

  • Live-cell imaging to track lytic granule and MTOC movement.
  • Perturbation experiments to assess the roles of actin, microtubules, and dynein motor proteins.
  • Analysis of the temporal sequence of cellular events.

Main Results:

  • Lytic granules rapidly converged at the MTOC, preceding MTOC polarization to the immunological synapse.
  • MTOC-directed lytic granule transport was independent of actin and microtubule dynamics.
  • This transport relied on dynein motor function and occurred before commitment to cytotoxicity.

Conclusions:

  • A novel paradigm of rapid, MTOC-directed transport of lytic granules is identified as a prerequisite for directed secretion.
  • This transport mechanism prepares NK cells for precise secretory functions but does not commit them to target cell killing.

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