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Role of very long fatty acid-containing glycosphingolipids in membrane organization and cell signaling: the model of lactosylceramide in neutrophils

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Abstract

Glycosphingolipids are highly enriched in specialized membrane microdomains (“lipid rafts”, caveolar domains and glycosynapses), and they participate to the process of transduction of information across the membrane. Lactosylceramide (LacCer) is specifically coupled with the Src family kinase Lyn in plasma membrane microdomains of human neutrophils. Ligand binding to LacCer activates Lyn, resulting in neutrophil functions, such as superoxide generation and migration. The β-Gal-(1–4)-β-Glc disaccharide structure of LacCer is necessary, but it is not sufficient for LacCer-mediated Lyn activation. For this function, the presence of a LacCer molecular species with ceramide containing a very long fatty acid chain is also required. In this manuscript, we discuss the importance of interdigitation within the membrane, promoted by the presence of glycosphingolipid species with very long fatty acyl chains as determinants for membrane organization, instrumental to the signaling process.

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References

  1. Hakomori, S.: Structure, organization, and function of glycosphingolipids in membrane. Curr. Opin. Hematol. 10, 16–24 (2003). doi:10.1097/00062752-200301000-00004

    Article  PubMed  CAS  Google Scholar 

  2. Sonnino, S., Prinetti, A., Mauri, L., Chigorno, V., Tettamanti, G.: Dynamic and structural properties of sphingolipids as driving forces for the formation of membrane domains. Chem. Rev. 106, 2111–2125 (2006). doi:10.1021/cr0100446

    Article  PubMed  CAS  Google Scholar 

  3. Hakomori, S., Handa, K., Iwabuchi, K., Yamamura, S., Prinetti, A.: New insights in glycosphingolipid function: “glycosignaling domain,” a cell surface assembly of glycosphingolipids with signal transducer molecules,involved in cell adhesion coupled with signaling. Glycobiology 8, xi–xix (1998)

    PubMed  CAS  Google Scholar 

  4. Sonnino, S., Mauri, L., Chigorno, V., Prinetti, A.: Gangliosides as components of lipid membrane domains. Glycobiology 17, 1R–13R (2007). doi:10.1093/glycob/cwl052

    Article  PubMed  CAS  Google Scholar 

  5. Palestini, P., Masserini, M., Sonnino, S., Giuliani, A., Tettamanti, G.: Changes in the ceramide composition of rat forebrain gangliosides with age. J. Neurochem. 54, 230–235 (1990). doi:10.1111/j.1471-4159.1990.tb13305.x

    Article  PubMed  CAS  Google Scholar 

  6. Prinetti, A., Chigorno, V., Prioni, S., Loberto, N., Marano, N., Tettamanti, G., Sonnino, S.: Changes in the lipid turnover, composition, and organization, as sphingolipid-enriched membrane domains, in rat cerebellar granule cells developing in vitro. J. Biol. Chem. 276, 21136–21145 (2001). doi:10.1074/jbc.M010666200

    Article  PubMed  CAS  Google Scholar 

  7. Pitto, M., Parenti, M., Guzzi, F., Magni, F., Palestini, P., Ravasi, D., Masserini, M.: Palmitic is the main fatty acid carried by lipids of detergent-resistant membrane fractions from neural and non-neural cells. Neurochem. Res. 27, 729–734 (2002). doi:10.1023/A:1020240520465

    Article  PubMed  CAS  Google Scholar 

  8. Tanford, C.: The hydrophobic effect: formation of micelles and biological membranes. Wiley, New York (1973)

    Google Scholar 

  9. Ruettinger, A., Kiselev, M.A., Hauss, T., Dante, S., Balagurov, A.M., Neubert, R.H.: Fatty acid interdigitation in stratum corneum model membranes: a neutron diffraction study. Eur. Biophys. J. 37(6), 759–771 (2008), July

    Article  PubMed  CAS  Google Scholar 

  10. Bouwstra, J.A., Ponec, M.: The skin barrier in healthy and diseased state. Biochim. Biophys. Acta 1758, 2080–2095 (2006). doi:10.1016/j.bbamem.2006.06.021

    Article  PubMed  CAS  Google Scholar 

  11. Schroeder, F., Nemecz, G., Wood, W.G., Joiner, C., Morrot, G., Ayraut-Jarrier, M., Devaux, P.F.: Transmembrane distribution of sterol in the human erythrocyte. Biochim. Biophys. Acta 1066, 183–192 (1991). doi:10.1016/0005-2736(91)90185-B

    Article  PubMed  CAS  Google Scholar 

  12. Igbavboa, U., Avdulov, N.A., Chochina, S.V., Wood, W.G.: Transbilayer distribution of cholesterol is modified in brain synaptic plasma membranes of knockout mice deficient in the low-density lipoprotein receptor, apolipoprotein E, or both proteins. J. Neurochem. 69, 1661–1667 (1997)

    Article  PubMed  CAS  Google Scholar 

  13. Iwabuchi, K., Nagaoka, I.: Lactosylceramide-enriched glycosphingolipid signaling domain mediates superoxide generation from human neutrophils. Blood 100, 1454–1464 (2002)

    PubMed  CAS  Google Scholar 

  14. Nakayama, H., Yoshizaki, F., Prinetti, A., Sonnino, S., Mauri, L., Takamori, K., Ogawa, H., Iwabuchi, K.: Lyn-coupled LacCer-enriched lipid rafts are required for CD11b/CD18-mediated neutrophil phagocytosis of nonopsonized microorganisms. J. Leukoc. Biol. 83, 728–741 (2008). doi:10.1189/jlb.0707478

    Article  PubMed  CAS  Google Scholar 

  15. Sato, T., Iwabuchi, K., Nagaoka, I., Adachi, Y., Ohno, N., Tamura, H., Seyama, K., Fukuchi, Y., Nakayama, H., Yoshizaki, F., Takamori, K., Ogawa, H.: Induction of human neutrophil chemotaxis by Candida albicans-derived beta-1,6-long glycoside side-chain-branched beta-glucan. J. Leukoc. Biol. 80, 204–211 (2006). doi:10.1189/jlb.0106069

    Article  PubMed  CAS  Google Scholar 

  16. Arnaout, M.A.: Structure and function of the leukocyte adhesion molecules CD11/CD18. Blood 75, 1037–1050 (1990)

    PubMed  CAS  Google Scholar 

  17. Altieri, D.C., Bader, R., Mannucci, P.M., Edgington, T.S.: Oligospecificity of the cellular adhesion receptor Mac-1 encompasses an inducible recognition specificity for fibrinogen. J. Cell Biol. 107, 1893–1900 (1988). doi:10.1083/jcb.107.5.1893

    Article  PubMed  CAS  Google Scholar 

  18. Detmers, P.A., Lo, S.K., Olsen-Egbert, E., Walz, A., Baggiolini, M., Cohn, Z.A.: Neutrophil-activating protein 1/interleukin 8 stimulates the binding activity of the leukocyte adhesion receptor CD11b/CD18 on human neutrophils. J. Exp. Med. 171, 1155–1162 (1990). doi:10.1084/jem.171.4.1155

    Article  PubMed  CAS  Google Scholar 

  19. Jones, S.L., Knaus, U.G., Bokoch, G.M., Brown, E.J.: Two signaling mechanisms for activation of alphaM beta2 avidity in polymorphonuclear neutrophils. J. Biol. Chem. 273, 10556–10566 (1998). doi:10.1074/jbc.273.17.10556

    Article  PubMed  CAS  Google Scholar 

  20. Weber, C., Kitayama, J., Springer, T.A.: Differential regulation of beta 1 and beta 2 integrin avidity by chemoattractants in eosinophils. Proc. Natl. Acad. Sci. USA 93, 10939–10944 (1996). doi:10.1073/pnas.93.20.10939

    Article  PubMed  CAS  Google Scholar 

  21. Fagerholm, S.C., Varis, M., Stefanidakis, M., Hilden, T.J., Gahmberg, C.G.: alpha-Chain phosphorylation of the human leukocyte CD11b/CD18 (Mac-1) integrin is pivotal for integrin activation to bind ICAMs and leukocyte extravasation. Blood 108, 3379–3386 (2006). doi:10.1182/blood-2006-03-013557

    Article  PubMed  CAS  Google Scholar 

  22. Piccardoni, P., Manarini, S., Federico, L., Bagoly, Z., Pecce, R., Martelli, N., Piccoli, A., Totani, L., Cerletti, C., Evangelista, V.: SRC-dependent outside-in signalling is a key step in the process of autoregulation of beta2 integrins in polymorphonuclear cells. Biochem. J. 380, 57–65 (2004). doi:10.1042/BJ20040151

    Article  PubMed  CAS  Google Scholar 

  23. Vetvicka, V., Thornton, B.P., Ross, G.D.: Soluble beta-glucan polysaccharide binding to the lectin site of neutrophil or natural killer cell complement receptor type 3 (CD11b/CD18) generates a primed state of the receptor capable of mediating cytotoxicity of iC3b-opsonized target cells. J. Clin. Invest. 98, 50–61 (1996). doi:10.1172/JCI118777

    Article  PubMed  CAS  Google Scholar 

  24. Evangelista, V., Pamuklar, Z., Piccoli, A., Manarini, S., Dell’elba, G., Pecce, R., Martelli, N., Federico, L., Rojas, M., Berton, G., Lowell, C.A., Totani, L., Smyth, S.S.: Src family kinases mediate neutrophil adhesion to adherent platelets. Blood 109, 2461–2469 (2007). doi:10.1182/blood-2006-06-029082

    Article  PubMed  CAS  Google Scholar 

  25. Rabb, H., Michishita, M., Sharma, C.P., Brown, D., Arnaout, M.A.: Cytoplasmic tails of human complement receptor type 3 (CR3, CD11b/CD18) regulate ligand avidity and the internalization of occupied receptors. J. Immunol. 151, 990–1002 (1993)

    PubMed  CAS  Google Scholar 

  26. Dedhar, S., Hannigan, G.E.: Integrin cytoplasmic interactions and bidirectional transmembrane signalling. Curr. Opin. Cell Biol. 8, 657–669 (1996). doi:10.1016/S0955-0674(96)80107-4

    Article  PubMed  CAS  Google Scholar 

  27. Riboni, L., Acquotti, D., Casellato, R., Ghidoni, R., Montagnolo, G., Benevento, A., Zecca, L., Rubino, F., Sonnino, S.: Changes of the human liver GM3 ganglioside molecular species during aging. Eur. J. Biochem. 203, 107–113 (1992). doi:10.1111/j.1432-1033.1992.tb19834.x

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This paper has been supported in part by University of Milan Grant 2006 to S.S., Fondazione Cariplo Grant 2006 to S.S, Mizutani Foundation for Glycosciences Grant 2007 to A.P. This study was also supported in part by a grant-in-aid for Scientific Research on Priority Areas (16017293) to K.I., and by “High-Tech Research Center” Project for Private Universities: matching fund subsidy from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

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Authors and Affiliations

  1. Dipartimento di Chimica, Biochimica e Biotecnologie per la Medicina, Università degli Studi di Milano, Via Fratelli Cervi 93, 20090, Segrate, Italy

    Sandro Sonnino & Alessandro Prinetti

  2. Institute for Environmental and Gender-specific Medicine, Juntendo University Graduate School of Medicine, Tomioka 2-1-1 Urayasu, Chiba, 279-0021, Japan

    Hitoshi Nakayama, Mitsuaki Yangida, Hideoki Ogawa & Kazuhisa Iwabuchi

Authors
  1. Sandro Sonnino
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  2. Alessandro Prinetti
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  3. Hitoshi Nakayama
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  4. Mitsuaki Yangida
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  5. Hideoki Ogawa
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  6. Kazuhisa Iwabuchi
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Correspondence to Sandro Sonnino or Kazuhisa Iwabuchi.

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Sonnino, S., Prinetti, A., Nakayama, H. et al. Role of very long fatty acid-containing glycosphingolipids in membrane organization and cell signaling: the model of lactosylceramide in neutrophils. Glycoconj J 26, 615–621 (2009). https://doi.org/10.1007/s10719-008-9215-8

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