Gene expression analysis of murine wt and Nbeal2 -/- bone marrow derived mast cells (BMMCs) w/o IL-33 treatment
The Neurobeachin-like 2 (Nbeal2) protein is a BEACH (beige and chediak-higashi) family member. Loss of function mutations of the human NBEAL2 gene result in development of the gray platelet syndrome (GPS) a bleeding disorder characterized by macrothrombocytopenia, splenomegaly, and paucity of Î±-granules in megakaryocytes, platelets, mast cells (MCs), neutrophils and NK cells. We found that Nbeal2 deficiency in MCs leads to an enhanced resistance to growth factor deprivation, dysregulated distribution of c-Kit and of the multidrug resistant protein-1 (ABCB1), as well as to a pro-inflammatory MC-phenotype. These characteristics are caused by a defective protein degradation machinery resulting in accumulation of RSK and ribosomal proteins (RPS). These data demonstrate that Nbeal2 prevents oncogenic transformation by controlling protein homeostasis (proteostasis) in MCs. Overall design: 16 samples in four groups: Nbeal2 -/- w/o IL-33: 4 samples; Nbeal2 -/- with IL-33: 4 samples; wildtype w/o IL-33: 4 samples; wildtype with IL-33: 4 samples.