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The Journal of Immunology, 2009, 182, 948-956
Copyright © 2009 by The American Association of Immunologists, Inc.
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A Dual Role for Talin in NK Cell Cytotoxicity: Activation of LFA-1-Mediated Cell Adhesion and Polarization of NK Cells1

Emily M. Mace*,{dagger}, Susan J. Monkley§, David R. Critchley§ and Fumio Takei2,*,{ddagger}

* Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; {dagger} Genetics Graduate Program and {ddagger} Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada; and § Department of Biochemistry, University of Leicester, Leicester, United Kingdom

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by grants from the Canadian Institutes of Health Research (to F.T.) and the Wellcome Trust (to D.R.C.).

2 Address correspondence and reprint requests to Dr. Fumio Takei, Terry Fox Laboratory, British Columbia Cancer Agency, 675 West 10th Street, Vancouver, British Columbia, V5Z 1L3, Canada. E-mail address: ftakei{at}bccrc.ca

3 Abbreviations used in this paper: MTOC, microtubule organizing center; PLL, poly-L-lysine; ES, embryonic stem; WT, wild type; KO, knockout; calcein AM, calcein acetoxymethyl ester; sICAM-1, soluble ICAM-1.


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