title: Expression, Function, and Molecular Properties of the Killer Receptor Ncr1-Noé.
abstract: NK cells kill various cells using activating receptors, such as the natural cytotoxicity receptors (NCRs). NKp46 is a major NCR and is the only NCR expressed in mice (denoted Ncr1). Using Ncr1-deficient mice (Ncr1(gfp/pfp)) we demonstrated that Ncr1 controls various pathologies, and that in its absence Ncr1-related functions are impaired. In 2012, another Ncr1-related mouse was generated, named Noé, in which a random mutation, W32R, in position 32, impaired the Ncr1-Noé cell surface expression. Interestingly, in the Noé mice, Ncr1-dependent deficiencies were not observed. Additionally, the Noé-NK cells were hyperactivated, probably due to increased Helios expression, and the Noé mice demonstrate increased clearance of influenza and murine CMV. In contrast, in the Ncr1(gfp/pfp) mice infection with influenza was lethal and we show in the present study no difference in murine CMV infection between Ncr1(gfp/pfp) and wild-type (WT) mice. Because the foremost difference between the Noé and Ncr1(gfp/gfp) mice is the presence of a mutated Ncr1-Noé protein, we studied its properties. We show that Ncr1-Noé and various other Ncr1 mutants in position 32 can be expressed on the surface, albeit slowly and unstably, and that ligand recognition and function of the various Ncr1-Noé is similar to the WT Ncr1. We further show that the glycosylation pattern of Ncr1-Noé is aberrant, that the Ncr1-Noé proteins accumulate in the endoplasmic reticulum, and that the expression of Ncr1-Noé proteins, but not WT Ncr1, leads to increased Helios expression. Thus, we suggest that the NK hyperactivated phenotype observed in the Noé mice might result from the presence of the Ncr1-Noé protein.
authors.affiliation: Lautenberg Center for General and Tumor Immunology, Hebrew University Hadassah Medical School, Jerusalem 91120, Israel;
authors.forename: Ariella
authors.initials: A
authors.lastname: Glasner
authors.affiliation: Department of Histology and Embryology Center for Proteomics, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia;
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Simic
authors.affiliation: Department of Histology and Embryology Center for Proteomics, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia;
authors.forename: Karmela
authors.initials: K
authors.lastname: Miklić
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel; and National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Roth
authors.affiliation: Lautenberg Center for General and Tumor Immunology, Hebrew University Hadassah Medical School, Jerusalem 91120, Israel;
authors.forename: Orit
authors.initials: O
authors.lastname: Berhani
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel; and.
authors.forename: Isam
authors.initials: I
authors.lastname: Khalaila
authors.affiliation: Department of Histology and Embryology Center for Proteomics, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia;
authors.forename: Stipan
authors.initials: S
authors.lastname: Jonjic
authors.affiliation: Lautenberg Center for General and Tumor Immunology, Hebrew University Hadassah Medical School, Jerusalem 91120, Israel; oferm@ekmd.huji.ac.il.
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D006031:Glycosylation; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000235:genetics / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology
chemical_list: D000950:Antigens, Ly; D004268:DNA-Binding Proteins; C111431:IKZF2 protein, human; C112260:NCR1 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; C118384:Ncr1 protein, mouse; D014157:Transcription Factors; C491746:Zfpn1a2 protein, mouse; D051740:Ikaros Transcription Factor