Lytic immune synapse function requires filamentous actin deconstruction by Coronin 1A.
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.
Center for Human Immunobiology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX 77030.
Emily M
EM
Mace
Jordan S
JS
Orange
D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D054992:Immunological Synapses / Q000276:immunology* / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D000097573:Red Fluorescent Protein
D000199:Actins; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D008840:Microfilament Proteins; D011993:Recombinant Fusion Proteins; D000097573:Red Fluorescent Protein; C072061:coronin proteins
cytotoxicity; natural killer cells; superresolution microscopy