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 super-resolution 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.