| First Author | Glasner A | Year | 2015 |
| Journal | J Immunol | Volume | 195 |
| Issue | 8 | Pages | 3959-69 |
| PubMed ID | 26371250 | Mgi Jnum | J:317869 |
| Mgi Id | MGI:6844118 | Doi | 10.4049/jimmunol.1501234 |
| Citation | Glasner A, et al. (2015) Expression, Function, and Molecular Properties of the Killer Receptor Ncr1-Noe. J Immunol 195(8):3959-69 |
| abstractText | 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 Noe, in which a random mutation, W32R, in position 32, impaired the Ncr1-Noe cell surface expression. Interestingly, in the Noe mice, Ncr1-dependent deficiencies were not observed. Additionally, the Noe-NK cells were hyperactivated, probably due to increased Helios expression, and the Noe 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 Noe and Ncr1(gfp/gfp) mice is the presence of a mutated Ncr1-Noe protein, we studied its properties. We show that Ncr1-Noe 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-Noe is similar to the WT Ncr1. We further show that the glycosylation pattern of Ncr1-Noe is aberrant, that the Ncr1-Noe proteins accumulate in the endoplasmic reticulum, and that the expression of Ncr1-Noe proteins, but not WT Ncr1, leads to increased Helios expression. Thus, we suggest that the NK hyperactivated phenotype observed in the Noe mice might result from the presence of the Ncr1-Noe protein. |
