Naslov
Expression, Function, and Molecular Properties of the Killer Receptor Ncr1-Noé

Autori
Glasner, A ; Šimić, Hrvoje, Miklić, Karmela ; Roth, Z ; Berhani, O ; Khalaila, I ; Jonjić, Stipan ; Mandelboim, O

Izvornik
Journal of immunology (0022-1767) 195 (2015), 8; 3959-3969

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Natural killer cells ; Cytomegalovirus ; NKp46/Ncr1 receptor ; Ncr1-Noe´ mutation

Sažetak
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 (Ncr1gfp/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 Ncr1gfp/pfp mice infection with influenza was lethal and we show in the present study no difference in murine CMV infection between Ncr1gfp/pfp and wild-type (WT) mice. Because the foremost difference between the Noe´ and Ncr1gfp/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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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