title: Expression and function of NKp46 W32R: the human homologous protein of mouse NKp46 W32R (Noé).
abstract: Natural killer (NK) cells eradicate infected cells and tumors following the triggering of activating receptors, like the Natural Cytotoxicity Receptors (NCRs), which include NKp30, NKp44 and NKp46. NKp46 is the only NCR expressed in mice (mNKp46), and except for some Innate Lymphoid Cell (ILC) populations (ILC1/3 subsets), its expression is restricted to NK cells. Previously, a mouse named Noé was generated in which a random point mutation (W32R) impaired the cell surface expression of mNKp46. Interestingly, the Noé mice NK cells expressed twice as much of the transcription factor Helios, and displayed general non-NKp46 specific hyperactivity. We recently showed that the mNKp46 W32R (Noé) protein was expressed on the surface of various cells; albeit slowly and unstably, that it is aberrantly glycosylated and accumulates in the ER. Interestingly, the Tryptophan (Trp) residue in position 32 is conserved between humans and mice. Therefore, we studied here the human orthologue protein of mNKp46 W32R, the human NKp46 W32R. We demonstrated that NKp46 W32R is aberrantly glycosylated, accumulates in the ER, and is unstable on the cell surface. Furthermore, we showed that overexpression of NKp46 W32R or Helios resulted in augmented NK cell activation, which may be applied to boost NK activity for therapeutic applications.
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, Jerusalem, 91120, Israel.
authors.forename: Ariella
authors.initials: A
authors.lastname: Glasner
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, Jerusalem, 91120, Israel.
authors.forename: Batya
authors.initials: B
authors.lastname: Isaacson
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, Jerusalem, 91120, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000737:chemistry; D004847:Epithelial Cells / Q000737:chemistry; D006031:Glycosylation; D022781:Hepatocytes / Q000737:chemistry; D006801:Humans; D007694:Killer Cells, Natural / Q000737:chemistry*; D008565:Membrane Proteins / Q000032:analysis; D050505:Mutant Proteins / Q000032:analysis* / Q000235:genetics* / Q000378:metabolism; D020125:Mutation, Missense; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000032:analysis* / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000737:chemistry
chemical_list: D008565:Membrane Proteins; D050505:Mutant Proteins; C112260:NCR1 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1