| RRC ID |
77358
|
| 著者 |
Mace EM, Monkley SJ, Critchley DR, Takei F.
|
| タイトル |
A dual role for talin in NK cell cytotoxicity: activation of LFA-1-mediated cell adhesion and polarization of NK cells.
|
| ジャーナル |
J Immunol
|
| Abstract |
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.
|
| 巻・号 |
182(2)
|
| ページ |
948-56
|
| 公開日 |
2009-1-15
|
| DOI |
10.4049/jimmunol.182.2.948
|
| PII |
182/2/948
|
| PMID |
19124737
|
| MeSH |
Actins / metabolism
Animals
Cell Adhesion / genetics
Cell Adhesion / immunology
Cell Line, Tumor
Cells, Cultured
Cytotoxicity, Immunologic* / genetics
Intercellular Adhesion Molecule-1 / metabolism
Killer Cells, Natural / cytology
Killer Cells, Natural / immunology*
Killer Cells, Natural / metabolism*
L Cells
Lymphocyte Activation / genetics
Lymphocyte Activation / immunology
Lymphocyte Function-Associated Antigen-1 / physiology*
Mice
Mice, Inbred C57BL
Mice, Knockout
Signal Transduction / genetics
Signal Transduction / immunology
Talin / deficiency
Talin / genetics
Talin / physiology*
|
| IF |
4.886
|
| リソース情報 |
| ヒト・動物細胞 |
OP9(RCB1124) |
