The Neurobeachin-like 2 Protein Regulates Mast Cell Homeostasis.
Sebastian DrubeRandy GrimlowskiCarsten DeppermannJulia FröbelFlorian KraftNico AndreasDavid StegnerJan DudeckFranziska WeberMandy RödigerChristiane GöpfertJulia DrubeDaniela ReichBernhard NieswandtAnne DudeckThomas KamradtPublished in: Journal of immunology (Baltimore, Md. : 1950) (2017)
The neurobeachin-like 2 protein (Nbeal2) belongs to the family of beige and Chediak-Higashi (BEACH) domain proteins. Loss-of-function mutations in the human NBEAL2 gene or Nbeal2 deficiency in mice cause gray platelet syndrome, a bleeding disorder characterized by macrothrombocytopenia, splenomegaly, and paucity of α-granules in megakaryocytes and platelets. We found that in mast cells, Nbeal2 regulates the activation of the Shp1-STAT5 signaling axis and the composition of the c-Kit/STAT signalosome. Furthermore, Nbeal2 mediates granule formation and restricts the expression of the transcription factors, IRF8, GATA2, and MITF as well as of the cell-cycle inhibitor p27, which are essential for mast cell differentiation, proliferation, and cytokine production. These data demonstrate the relevance of Nbeal2 in mast cells above and beyond granule biosynthesis.
Keyphrases
- cell cycle
- cell proliferation
- transcription factor
- endothelial cells
- poor prognosis
- signaling pathway
- atrial fibrillation
- genome wide
- gene expression
- metabolic syndrome
- high fat diet induced
- genome wide identification
- skeletal muscle
- adipose tissue
- copy number
- big data
- induced pluripotent stem cells
- cell wall
- replacement therapy