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The zebrafish activating immune receptor Nitr9 signals via Dap12

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Abstract

Both inhibitory and activating forms of natural killer (NK) cell receptors are found in mammals. The activating receptors play a direct role in the recognition of virally infected or transformed cells and transduce activating signals into the cell by partnering with an adaptor protein, which contains a cytoplasmic activation motif. Activating NK receptors encoded by the mammalian leukocyte receptor complex (e.g., killer cell immunoglobulin-like receptors) and the natural killer complex (e.g., Ly49s) partner with the adaptor protein DAP12, whereas NK receptors encoded in the CD94/NKG2 complex partner with the adaptor protein DAP10. Novel immune-type receptors (NITRs) found in bony fish share several common features with immunoglobulin-type NK receptors. Nitr9 is a putative activating receptor in zebrafish that induces cytotoxicity within the context of human NK cells. One isoform of Nitr9, Nitr9L, is shown here to preferentially partner with a zebrafish ortholog of Dap12. Cross-linking the Nitr9L–Dap12 complex results in activation of the phosphytidylinositol 3-kinase→AKT→extracellular signal-regulated kinase pathway suggesting that the DAP12-based activating pathway is conserved between bony fish and mammals.

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Acknowledgments

We thank P.K. Epling-Burnette for helpful discussions and Barb Pryor for editorial assistance. Sequence data (nitr9 super short isoform) from this article have been deposited with the GenBank database under accession number EF690658. This research was supported by grants awarded by NIH R01 AI057559 (GWL) and R01 AI056213 (SW), NSF MCB-0505585 (JAY), and the All Children’s Hospital Foundation (GWL).

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Authors and Affiliations

  1. Immunology Program, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Avenue, Tampa, FL, 33612, USA

    Sheng Wei, Jun-min Zhou, Xinghong Chen, Jinhong Liu, Julie Y. Djeu & Gary W. Litman

  2. Department of Molecular Biomedical Sciences and Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC, 27606, USA

    Radhika N. Shah, Timothy M. Orcutt & Jeffrey A. Yoder

  3. Immunology Program, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC, 27606, USA

    Radhika N. Shah & Jeffrey A. Yoder

  4. Division of Biological Sciences, Section of Cell and Developmental Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA

    David Traver

  5. Department of Molecular Genetics, All Children’s Hospital, 801 Sixth Street South, St. Petersburg, FL, 33701, USA

    Gary W. Litman

  6. Department of Pediatrics, University of South Florida College of Medicine, University of South Florida/All Children’s Hospital Children’s Research Institute, 830 First Street South, St. Petersburg, FL, 33701, USA

    Gary W. Litman

Authors
  1. Sheng Wei
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  2. Jun-min Zhou
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  3. Xinghong Chen
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  4. Radhika N. Shah
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  5. Jinhong Liu
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  6. Timothy M. Orcutt
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  7. David Traver
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  8. Julie Y. Djeu
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  9. Gary W. Litman
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  10. Jeffrey A. Yoder
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Corresponding author

Correspondence to Jeffrey A. Yoder.

Additional information

Sheng Wei and Jun-min Zhou contributed equally to this work.

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Wei, S., Zhou, Jm., Chen, X. et al. The zebrafish activating immune receptor Nitr9 signals via Dap12. Immunogenetics 59, 813–821 (2007). https://doi.org/10.1007/s00251-007-0250-6

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  • DOI: https://doi.org/10.1007/s00251-007-0250-6

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