Molecular regulation of the plasma membrane-proximal cellular steps involved in NK cell cytolytic function

Prasad V. Phatarpekar, Daniel D. Billadeau

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Natural killer (NK) cells, cytolytic lymphocytes of the innate immune system, play a crucial role in the immune response against infection and cancer. NK cells kill target cells through exocytosis of lytic granules that contain cytotoxic proteins, such as perforin and granzymes. Formation of a functional immune synapse, i.e. the interface between the NK cell and its target cell enhances lysis through accumulation of polymerized F-actin at the NK cell synapse, leading to convergence of lytic granules to the microtubule organizing center (MTOC) and its subsequent polarization along microtubules to deliver the lytic granules to the synapse. In this review, we focus on the molecular mechanisms regulating the cellular processes that occur after the lytic granules are delivered to the cytotoxic synapse. We outline how – once near the synapse – the granules traverse the clearings created by F-actin remodeling to dock, tether and fuse with the plasma membrane in order to secrete their lytic content into the synaptic cleft through exocytosis. Further emphasis is given to the role of Ca2+ mobilization during degranulation and, whenever applicable, we compare these mechanisms in NK cells and cytotoxic T lymphocytes (CTLs) as adaptive immune system effectors.

Original languageEnglish (US)
Article numberjcs240424
JournalJournal of cell science
Issue number5
StatePublished - Mar 2020


  • Exocytosis
  • Immune deficiency
  • Lytic granule
  • Natural killer cell

ASJC Scopus subject areas

  • Cell Biology


Dive into the research topics of 'Molecular regulation of the plasma membrane-proximal cellular steps involved in NK cell cytolytic function'. Together they form a unique fingerprint.

Cite this