GD1b-Derived Gangliosides Modulate FcεRI Endocytosis in Mast Cells

Abstract

The role of the mast cell–specific gangliosides in the modulation of the endocytic pathway of FcεRI was investigated in RBL-2H3 cells and in the ganglioside-deficient cell lines, E5 and D1. MAb BC4, which binds to the α subunit of FcεRI, was used in the analysis of receptor internalization. After incubation with BC4-FITC for 30 min, endocytic vesicles in RBL-2H3 and E5 cells were dispersed in the cytoplasm. After 1 hr, the endocytic vesicles of the RBL-2H3 cells had fused and formed clusters, whereas in the E5 cells, the fusion was slower. In contrast, in D1 cells, the endocytic vesicles were smaller and remained close to the plasma membrane even after 3 hr of incubation. When incubated with BC4-FITC and subsequently imunolabeled for markers of various endocytic compartments, a defect in the endocytic pathway in the E5 and D1 cells became evident. In the D1 cells, this defect was observed at the initial steps of endocytosis. Therefore, the ganglioside derivatives from GD1b are important in the endocytosis of FcεRI in mast cells. Because gangliosides may play a role in mast cell–related disease processes, they provide an attractive target for drug therapy and diagnosis.

Antiproliferative Effects of Fluoxetine on Colon Cancer Cells and in a Colonic Carcinogen Mouse Model

“…According to previous description [5], [27], IHC and IMF staining were performed on paraffin colonic sections (4 µm). Primary antibodies were purchased from Novocastra (USA), Santa Cruz Biotechnology (Germany), and Biocare Medical (USA).…”

Proteomic Analysis of Lipid Rafts from RBL-2H3 Mast Cells

“…Mast cells (MCs) are multifunctional immune cells that, in addition to their well-established role in allergic and anaphylactic reactions, are implicated in innate and adaptive immunity, and in inflammation among other physiological and pathological processes [28,29,30]. Lipid rafts modulate many important biological processes related to these MC functions, such as degranulation, endocytosis, play a role in MC development and recruitment, and contribute to the preservation of MC structure and organization [6,31,32,33]. However, there is no MC lipid raft proteome available.…”

n-3 Polyunsaturated fatty acids and mast cell activation

“…In stimulated mast cells, GD1b (a ganglioside) in lipid rafts was shown to be internalized together with Fc«RI in the same vesicle and to follow the same path to the lysosomes [175]. In addition, GD1b deficiency suppressed Fc«RI ubiquitination and endocytosis in mast cells [176]. These results indicate that lipid rafts might not only facilitate the tagging of Fc«RI for internalization, but also function as the site of vesicle formation.…”