TY - JOUR
T1 - CD56 regulates human NK cell cytotoxicity through Pyk2
AU - Gunesch, Justin T.
AU - Dixon, Amera L.
AU - Ebrahim, Tasneem A.M.
AU - Berrien-Elliott, Melissa M.
AU - Tatineni, Swetha
AU - Kumar, Tejas
AU - Hegewisch-Solloa, Everardo
AU - Fehniger, Todd A.
AU - Mace, Emily M.
N1 - Funding Information:
This work was supported in part by R01AI137073 to EMM. The authors have no competing interests to declare. We thank the Genome Engineering and iPSC Center (GEiC) at the Washington University in St. Louis for gRNA validation services. National Institutes of Health R01AI137073 Emily M Mace National Institutes of Health R01CA205239 Todd A Fehniger National Institutes of Health P50CA171063 Todd A Fehniger Melissa M Berrien-Elliott National Institutes of Health K12CA167540 Melissa M Berrien-Elliott.
Publisher Copyright:
© Gunesch et al.
PY - 2020/6
Y1 - 2020/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85087984876&partnerID=8YFLogxK
U2 - 10.7554/eLife.57346
DO - 10.7554/eLife.57346
M3 - Article
C2 - 32510326
AN - SCOPUS:85087984876
SN - 2050-084X
VL - 9
SP - 1
EP - 28
JO - eLife
JF - eLife
M1 - e57346
ER -