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

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 languageEnglish
Article number15036
JournalCell Discovery
Volume1
DOIs
StatePublished - 22 Dec 2015

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