Lytic immune synapse function requires filamentous actin deconstruction by Coronin 1A

Proc Natl Acad Sci U S A. 2014 May 6;111(18):6708-13. doi: 10.1073/pnas.1314975111. Epub 2014 Apr 23.


Lytic immune effector function depends upon directed secretion of cytolytic granules at the immunological synapse (IS) and requires dynamic rearrangement of filamentous (F)-actin. Coronin 1A (Coro1A) is the hematopoietic-specific member of the Coronin family of actin regulators that promote F-actin disassembly. Here, we show that Coro1A is required for natural killer (NK) cell cytotoxic function in two human NK cell lines and ex vivo cells from a Coro1A-deficient patient. Using superresolution nanoscopy to probe the IS, we demonstrate that Coro1A promotes the deconstruction of F-actin density that facilitates effective delivery of lytic granules to the IS. Thus, we show, for the first time to our knowledge, a critical role for F-actin deconstruction in cytotoxic function and immunological secretion and identify Coro1A as its mediator.

Keywords: cytotoxicity; natural killer cells; superresolution microscopy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / chemistry
  • Actins / metabolism*
  • Cell Line
  • Cytotoxicity, Immunologic
  • Gene Knockdown Techniques
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Immunological Synapses / immunology*
  • Immunological Synapses / metabolism*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Luminescent Proteins / metabolism
  • Microfilament Proteins / deficiency
  • Microfilament Proteins / immunology*
  • Microfilament Proteins / metabolism*
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / metabolism


  • Actins
  • Luminescent Proteins
  • Microfilament Proteins
  • Recombinant Fusion Proteins
  • red fluorescent protein
  • coronin proteins
  • Green Fluorescent Proteins