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Ezrin is a negative regulator of death receptor-induced apoptosis

Oncogene volume 29, pages 1374–1383 (2010)Cite this article

Abstract

Ezrin links cortical actin filaments with the cell membrane, and has a critical role in many membrane-initiated events. Fas is directly associated with ezrin, but conflicting results have been reported for the involvement of ezrin in Fas-induced cell death. In this study we show that ezrin was associated with Fas in T cells before stimulation and was released shortly after Fas ligand (FasL) engagement. The knockdown of ezrin moderately increased Fas-triggered or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-triggered cell death in normal T lymphocytes and in H9 cells, but had no effect on death receptor-induced apoptosis in type II cells, such as Jurkat and CEM. Expression of a dominant-negative form of ezrin also led to an increased Fas-induced apoptosis in H9 cells. Ezrin deficiency did not affect the internalization of Fas after Fas ligation. Instead, an enhanced formation of death-inducing signaling complex (DISC) was observed in H9 cells with ezrin knockdown, leading to accelerated caspase-8 activation. Together, our results suggest that ezrin has a negative role in the recruitment of Fas into signaling complexes in type I T cells. Loss of ezrin likely removes the constraint imposed by ezrin and facilitates the assembly of death receptor complex in T cells.

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Abbreviations

DISC:

death-inducing signaling complex

ERM:

ezrin, radixin and moesin

FasL:

Fas ligand

IS:

immunological synapse

TRAIL:

tumor necrosis factor-related apoptosis-inducing ligand

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Acknowledgements

This work was supported by Grant NHRI-EX96–9527NI from National Health Research Institute, NSC 95–2320-B001–023 from National Science Council and an Academia Sinica Investigator Award from Academia Sinica, Taiwan, ROC. We thank Drs I-Chen Ho, Gina Costa and Garry Nolan for critical reagents, Yamin Lin and FACS Core of Institute of Molecular Biology, Academia Sinica for cell sorting and Dr Harry Wilson for editing this paper.

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Authors and Affiliations

  1. Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan

    W-C Kuo, S-L Hsieh & M-Z Lai

  2. Institute of Molecular Biology,

    W-C Kuo, K-T Yang & M-Z Lai

  3. Academia Sinica, Taipei, Taiwan

    W-C Kuo, K-T Yang & M-Z Lai

  4. Genomic Research Center, Academia Sinica, Taipei, Taiwan

    S-L Hsieh

  5. Institute of Immunology, National Taiwan University, Taipei, Taiwan

    M-Z Lai

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  1. W-C Kuo
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Correspondence to M-Z Lai.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Kuo, WC., Yang, KT., Hsieh, SL. et al. Ezrin is a negative regulator of death receptor-induced apoptosis. Oncogene 29, 1374–1383 (2010). https://doi.org/10.1038/onc.2009.417

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