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

Ariella Glasner1, Ziv Roth2, Alexander Varvak3

  • 1The Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, The Institute of Medical Research Israel Canada (IMRIC) , Jerusalem, Israel.

Cell Discovery
|July 28, 2016
PubMed

Insights

Mouse Ncr1, a key natural killer cell receptor, possesses novel O-glycosylations essential for its function. These findings reveal new insights into NK cell receptor activity and regulation.

Area of Science:

  • Immunology
  • Cell Biology
  • Glycobiology

Background:

  • Natural killer (NK) cells are crucial for innate immunity, eliminating tumor and virus-infected cells via activating receptors.
  • NKp46 (human) and its mouse ortholog, Ncr1, are key activating NK cell receptors involved in various pathologies.
  • While human NKp46 requires O- and N-glycosylations for activity, mouse Ncr1 was predicted to have only N-linked glycosylations.

Purpose of the Study:

  • To investigate the glycosylation patterns of mouse Ncr1.
  • To determine the functional significance of Ncr1 glycosylations in NK cell activity.

Main Methods:

  • Computational prediction algorithms and high-performance liquid chromatography (HPLC) for glycosylation analysis.
  • Surface plasmon resonance (SPR), biochemical assays, mutational analysis.
  • In vitro and in vivo functional assays to assess Ncr1 activity.

Main Results:

  • Discovery of two novel putative O-glycosylations on mouse Ncr1, with one conserved in human NKp46 (Thr 225).
  • Demonstration that these O-glycosylations are critical for Ncr1 function.
  • Evidence that Ncr1 glycosylation differs significantly from initial predictions.

Conclusions:

  • Mouse Ncr1 possesses previously unrecognized O-glycosylations essential for its role in NK cell-mediated immunity.
  • These findings highlight the importance of glycosylation in regulating NK cell receptor function and provide a basis for further research into NK cell activation mechanisms.