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Membrane microdomains in immunity: Glycosphingolipid-enriched domain-mediated innate immune responses

Authors

  • Kazuhisa Iwabuchi,

    Corresponding author
    1. Institute for Environmental and Gender-specific Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
    2. Laboratory for Biochemistry, Juntendo University Faculty of Health Care and Nursing, Tokyo, Japan
    • Institute for Environmental and Gender-specific Medicine, Juntendo University Graduate School of Medicine, Japan
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    • Tel.: +81 47 353 3171; Fax: +81 47 353 3178

  • Hitoshi Nakayama,

    1. Laboratory for Biochemistry, Juntendo University Faculty of Health Care and Nursing, Tokyo, Japan
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  • Hiromi Masuda,

    1. Institute for Environmental and Gender-specific Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
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  • Katsunari Kina,

    1. Institute for Environmental and Gender-specific Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
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  • Hideoki Ogawa,

    1. Institute for Environmental and Gender-specific Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
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  • Kenji Takamori

    1. Institute for Environmental and Gender-specific Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
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  • This article was published online on 10 April 2012. An error was subsequently identified. This notice is included in the online and print versions to indicate that both have been corrected on 2 May 2012.

Abstract

Over the last 30 years, many studies have indicated that glycosphingolipids (GSLs) expressed on the cell surface may act as binding sites for microorganisms. Based on their physicochemical characteristics, GSLs form membrane microdomains with cholesterol, sphingomyelin, glycosylphosphatidylinositol (GPI)-anchored proteins, and various signaling molecules, and GSL-enriched domains have been shown to be involved in these defense responses. Among the GSLs, lactosylceramide (LacCer, CDw17) can bind to various microorganisms. LacCer is expressed at high levels on the plasma membrane of human neutrophils, and forms membrane microdomains associated with the Src family tyrosine kinase Lyn. LacCer-enriched membrane microdomains mediate superoxide generation, chemotaxis, and non-opsonic phagocytosis. Therefore, LacCer-enriched membrane microdomains are thought to function as pattern recognition receptors (PRRs) to recognize pathogen-associated molecular patterns (PAMPs) expressed on microorganisms. In contrast, several pathogens have developed infection mechanisms using membrane microdomains. In addition, some pathogens have the ability to avoid degradation by escaping from the vacuolar compartment or preventing phagosome maturation, utilizing membrane microdomains, such as LacCer-enriched domains, of host cells. The detailed molecular mechanisms of these membrane microdomain-associated host-pathogen interactions remain to be elucidated. © 2012 International Union of Biochemistry and Molecular Biology, Inc.

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