Identification of putative novel O-glycosylations in the NK killer receptor Ncr1 essential for its activity

Ariella Glasner, Ziv Roth, Alexander Varvak, Antonija Miletic, Batya Isaacson, Yotam Bar-On, Stipan Jonjic, Isam Khalaila, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Natural killer (NK) cells kill tumor and virus-infected cells using activating NK cell receptors. One of the major NK-activating receptors is NKp46 and its mouse ortholog Ncr1. NKp46/Ncr1 is expressed exclusively on NK cells and on a subset of innate lymphoid cells. NKp46/Ncr1 was shown to be involved in a myriad of pathologies and immunological settings. Specifically, NKp46/Ncr1 was shown to interact with the viral hemagglutinin (HA) protein and with an unknown tumor/cellular ligand. NKp46 and Ncr1 are structurally similar; however, they are substantially different in their glycosylation patterns. Although the human NKp46 carries both O- and N-glycosylations that are essential for its activity, the mouse Ncr1 was predicted to have N-linked glycosylations only. Here we discovered using prediction algorithms and high-performance liquid chromatography analysis that Ncr1 carries two putative novel O-glycosylations, one of which (Thr 225) is conserved in NKp46. We next used surface plasmon resonance, biochemical, mutational and functional in vitro and in vivo assays to demonstrate that the putative O-glycosylations of Ncr1 are critical for its function.

Original languageAmerican English
Article number15036
JournalCell Discovery
Volume1
DOIs
StatePublished - 22 Dec 2015

Bibliographical note

Funding Information:
This study was supported by the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement number 320473-BacNK. Further support came from the I-CORE Program of the Planning and Budgeting Committee and the Israel Science Foundation and by the I-Core on Chromatin and RNA in Gene Regulation, the GIF foundation, the Lewis family foundation, the ICRF professorship grant, the Israeli Science Foundation, the Helmholtz Israel grant and the Rosetrees Trust (all to OM). OM is a Crown Professor of Molecular Immunology. SJ is supported by the ERC Advanced Grant (Grant number: 322693).

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