The alpha-galactosyl derivatives of ganglioside GD(1b) are essential for the organization of lipid rafts in RBL-2H3 mast cells |
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Authors: | Silveira e Souza Adriana Maria Mariano Mazucato Vivian Marino de Castro Rodrigo Orlandini Matioli Fabiana Ciancaglini Pietro de Paiva Paulino Tony Jamur Maria Célia Oliver Constance |
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Institution: | aDepartment of Cell and Molecular Biology and Pathogenic Bioagents, Faculdade de Medicina de Ribeirão Preto – Universidade de São Paulo, Ribeirão Preto, SP, Brazil;bDepartment of Chemistry, Faculdade de Filosofia Ciências e Letras – Universidade de São Paulo, Ribeirão Preto, SP, Brazil |
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Abstract: | Gangliosides are complex glycosphingolipids that are important in many biological processes. The present study investigated the role of gangliosides in the organization of lipid rafts in RBL-2H3 mast cells and in the modulation of mast cell degranulation via FcRI. The role of gangliosides was examined using two ganglioside deficient cell lines (B6A4A2III-E5 and B6A4C1III-D1) as well as the parent cell line (RBL-2H3). All three cell lines examined express FcRI, Lyn, Syk and LAT. However, only in RBL-2H3 cells were FcRI, LAT and α-galactosyl derivatives of ganglioside GD1b mobilized to lipid raft domains following FcRI stimulation. The inhibition of glycosphingolipid synthesis in RBL-2H3 cells also resulted in a decrease in the release of β-hexosaminidase activity after FcRI activation. The two mutant cell lines have a reduced release of β-hexosaminidase activity after FcRI stimulation, but not after exposure to calcium ionophore. These results indicate that the α-galactosyl derivatives of ganglioside GD1b are important in the initial events of FcRI signaling upstream of Ca2+ influx. Since the initial signaling events occur in lipid rafts and in the mutant cell lines the rafts are disorganized, these results also suggest that these gangliosides contribute to the correct assembly of lipid rafts and are essential for mast cell activation via FcRI. |
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Keywords: | Mast cells Fcsciencedirect com/scidirimg/entities/25b RI" target="_blank">gif" alt="var epsilon" title="var epsilon" border="0">RI Lipid rafts Gangliosides Degranulation |
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