CD56 regulates human NK cell cytotoxicity through Pyk2
Justin T Gunesch,
Amera L Dixon,
Tasneem AM Ebrahim,
Melissa M Berrien-Elliott,
Swetha Tatineni,
Tejas Kumar,
Everardo Hegewisch-Solloa,
Todd A Fehniger,
Emily M Mace
Affiliations
Justin T Gunesch
Baylor College of Medicine, Houston, United States
Amera L Dixon
Baylor College of Medicine, Houston, United States; Rice University, Houston, United States; Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, United States
Tasneem AM Ebrahim
Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, United States; Barnard College, New York, United States
Melissa M Berrien-Elliott
Washington University School of Medicine, St. Louis, United States
Swetha Tatineni
Rice University, Houston, United States
Tejas Kumar
Rice University, Houston, United States
Everardo Hegewisch-Solloa
Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, United States
Human natural killer (NK) cells are defined as CD56+CD3−. Despite its ubiquitous expression on human NK cells the role of CD56 (NCAM) in human NK cell cytotoxic function has not been defined. In non-immune cells, NCAM can induce signaling, mediate adhesion, and promote exocytosis through interactions with focal adhesion kinase (FAK). Here we demonstrate that deletion of CD56 on the NK92 cell line leads to impaired cytotoxic function. CD56-knockout (KO) cells fail to polarize during immunological synapse (IS) formation and have severely impaired exocytosis of lytic granules. Phosphorylation of the FAK family member Pyk2 at tyrosine 402 is decreased in NK92 CD56-KO cells, demonstrating a functional link between CD56 and signaling in human NK cells. Cytotoxicity, lytic granule exocytosis, and the phosphorylation of Pyk2 are rescued by the reintroduction of CD56. These data highlight a novel functional role for CD56 in stimulating exocytosis and promoting cytotoxicity in human NK cells.
