A dual role for talin in NK cell cytotoxicity: activation of LFA-1-mediated cell adhesion and polarization of NK cells.
LFA-1 is critical for NK cell cytotoxicity because it mediates adhesion of NK cells to target cells. Talin is thought to associate with the cytoplasmic tail of LFA-1 and activates its ligand-binding function. In this study, we report that talin is also required for LFA-1-mediated outside-in signaling leading to NK cell polarization. NK cells generated from talin1-deficient murine embryonic stem cells are defective in LFA-1-mediated adhesion. Although exogenously added manganese activates LFA-1 on talin-deficient NK cells and induces conjugate formation with target cells, their LFA-1-dependent cytotoxicity is impaired. Binding of ICAM-1-coated beads to wild-type NK cells induces reorganization of the actin cytoskeleton and coligation of the activating receptor NKG2D induces polarization of cytotoxic granules, whereas talin1-deficient NK cells fail to polarize with or without NKG2D coligation. Thus, talin1 plays a dual role in NK cell cytotoxicity, first by activation of LFA-1-mediated adhesion and then via LFA-1-induced NK cell polarization.
Mace
Emily M
EM
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
Monkley
Susan J
SJ
Critchley
David R
DR
Takei
Fumio
F
D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D007739:L Cells; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D016608:Talin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D000199:Actins; D016169:Lymphocyte Function-Associated Antigen-1; D016608:Talin; C496077:Tln1 protein, mouse; D018799:Intercellular Adhesion Molecule-1