Role of glycosphingolipid-enriched microdomains in innate immunity: Microdomain-dependent phagocytic cell functions

Yoshizaki, Fumiko; Nakayama, Hitoshi; Iwahara, Chihiro; Takamori, Kenji; Ogawa, Hideoki; Iwabuchi, Kazuhisa

doi:10.1016/j.bbagen.2007.11.004

Cited by 55 publications

(51 citation statements)

References 90 publications

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“…A type of fungal ␤-glucans, derived from Candida albicans etc., specifically bound to LacCer and enhanced neutrophil functions, including chemotaxis (54). LPS and IFN-␥ treatment increased intracellular LacCer, which mediated iNOS gene expression in primary rat astrocytes (55).…”

Section: Discussionmentioning

confidence: 99%

Transmembrane BAX Inhibitor Motif Containing (TMBIM) Family Proteins Perturbs a trans-Golgi Network Enzyme, Gb3 Synthase, and Reduces Gb3 Biosynthesis

Yamaji

Nishikawa

Hanada

2010

Journal of Biological Chemistry

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Globotriaosylceramide (Gb3) is a well known receptor for Shiga toxin (Stx), produced by enterohemorrhagic Escherichia coli and Shigella dysenteriae. The expression of Gb3 also affects several diseases, including cancer metastasis and Fabry disease, which prompted us to look for factors involved in its metabolism. In the present study, we isolated two cDNAs that conferred resistance to Stx-induced cell death in HeLa cells by expression cloning: ganglioside GM3 synthase and the COOH terminus region of glutamate receptor, ionotropic, N-methyl-D-asparateassociated protein 1 (GRINA), a member of the transmembrane BAX inhibitor motif containing (TMBIM) family. Overexpression of the truncated form, named GRINA-C, and some members of the full-length TMBIM family, including FAS inhibitory molecule 2 (FAIM2), reduced Gb3, and lactosylceramide was accumulated instead. The change of glycolipid composition was restored by overexpression of Gb3 synthase, suggesting that the synthase is affected by GRINA-C and FAIM2. Interestingly, the mRNA level of Gb3 synthase was unchanged. Rather, localization of the synthase as well as TGN46, a trans-Golgi network marker, was perturbed to form punctate structures, and degradation of the synthase in lysosomes was enhanced. Furthermore, GRINA-C was associated with Gb3 synthase. These observations may demonstrate a new type of posttranscriptional regulation of glycosyltransferases.

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Section: Discussionmentioning

confidence: 99%

Transmembrane BAX Inhibitor Motif Containing (TMBIM) Family Proteins Perturbs a trans-Golgi Network Enzyme, Gb3 Synthase, and Reduces Gb3 Biosynthesis

Yamaji

Nishikawa

Hanada

2010

Journal of Biological Chemistry

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“…In fact, less than 10-30 separate proteins may reside in any given raft compartment at one time (51). Therefore, we measured the protein content of each fraction.…”

Section: Protein Concentration Across Fractionsmentioning

confidence: 99%

Isolation of rafts from mouse brain tissue by a detergent-free method

Persaud-Sawin

Lightcap

Harry

2009

Journal of Lipid Research

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Membrane rafts are rich in cholesterol and sphingolipids and have specific proteins associated with them. Due to their small size, their identification and isolation have proved to be problematic. Their insolubility in nonionic detergents, such as Triton-X 100, at 4°C has been the most common means of isolation. However, detergent presence can produce artifacts or interfere with ganglioside distribution. The direction is therefore toward the use of detergent-free protocols. We report an optimized method of raft isolation from lipid-rich brain tissue using a detergentfree method. We compared this to Triton-X 100-based isolation along sucrose or Optiprep™ gradients using the following endpoints: low protein content, high cholesterol content, presence of Flotillin 1 (Flot1), and absence of transferrin receptor (TfR) proteins. These criteria were met in raft fractions isolated in a detergent-free buffer along a sucrose gradient of 5%/35%/42.5%. The use of optiprep gave less consistent results with respect to protein distribution. We demonstrate that clean raft fractions with minimal myelin contamination can be reproducibly obtained in the top three low-density fractions along a sucrose step gradient.-Persaud-Sawin, D-A., S. Lightcap, and G. J. Harry. Isolation of rafts from mouse brain tissue by a detergent-free method.

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“…Lipid rafts act as signal transduction platforms for a variety of intracellular processes. 20 However, the precise location and molecular interactions between Lyn and CXCR4 in CML are unknown.…”

Section: Introductionmentioning

confidence: 99%

Role of stromal microenvironment in nonpharmacological resistance of CML to imatinib through Lyn/CXCR4 interactions in lipid rafts

et al. 2011

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We and others have previously demonstrated that p210 Bcr-Abl tyrosine kinase inhibits stromal cell-derived factor-1a/CXCR4 chemokine receptor signaling, contributing to the deficient adhesion of chronic myeloid leukemia (CML) cells to bone marrow stroma. Conversely, exposure of CML cells to a tyrosine kinase inhibitor (TKI) enhances migration of CML cells towards stromal cell layers and promotes non-pharmacological resistance to imatinib. Src-related kinase Lyn is known to interact with CXCL12/ CXCR4 signaling and is directly activated by p210 Bcr-Abl. In this study, we demonstrate that TKI treatment promoted CXCR4 redistribution into the lipid raft fraction, in which it co-localized with active phosphorylated form of Lyn (LynTyr396) in CML cells. Lyn inhibition or cholesterol depletion abrogated imatinib-induced migration, and dual Src/Abl kinase inhibitor dasatinib induced fewer CML cells to migrate to the stroma. These findings demonstrate the novel mechanism of microenvironmentmediated resistance through lipid raft modulation, which involves compartmental changes of the multivalent CXCR4 and Lyn complex. We propose that pharmacological targeting of lipid rafts may eliminate bone marrow-resident CML cells through interference with microenvironment-mediated resistance.

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Role of glycosphingolipid-enriched microdomains in innate immunity: Microdomain-dependent phagocytic cell functions

Cited by 55 publications

References 90 publications

Transmembrane BAX Inhibitor Motif Containing (TMBIM) Family Proteins Perturbs a trans-Golgi Network Enzyme, Gb3 Synthase, and Reduces Gb3 Biosynthesis

Transmembrane BAX Inhibitor Motif Containing (TMBIM) Family Proteins Perturbs a trans-Golgi Network Enzyme, Gb3 Synthase, and Reduces Gb3 Biosynthesis

Isolation of rafts from mouse brain tissue by a detergent-free method

Role of stromal microenvironment in nonpharmacological resistance of CML to imatinib through Lyn/CXCR4 interactions in lipid rafts

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