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

作者：Mace Emily M; Orange Jordan S^*

来源：Proceedings of the National Academy of Sciences, 2014, 111(18): 6708-6713.

DOI：10.1073/pnas.1314975111

• cytotoxicity
• superresolution microscopy
• natural killer cells

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.

• 出版日期2014-5-6