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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 synapse function requires filamentous actin deconstruction by Coronin 1A.

Author information

1
Center for Human Immunobiology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX 77030.

Abstract

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

PMID:
24760828
PMCID:
PMC4020046
DOI:
10.1073/pnas.1314975111
[Indexed for MEDLINE]
Free PMC Article

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