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FASEB J. 2017 Apr;31(4):1301-1322. doi: 10.1096/fj.201500075R. Epub 2016 Aug 4.

A novel sphingomyelin/cholesterol domain-specific probe reveals the dynamics of the membrane domains during virus release and in Niemann-Pick type C.

Author information

1
Rikagaku Kenkyūsho (RIKEN), Saitama, Japan.
2
Université Lyon 1, INSERM, Unité 1060, Villeurbanne, France.
3
Faculty of Core Research, Natural Science Division, Ochanomizu University, Tokyo, Japan.
4
Yukiguni Maitake Co., Limited, Niigata, Japan.
5
Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
6
Daiichi Sankyo Co., Limited, Tokyo, Japan.
7
Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia.
8
Graduate School of Humanities and Life Sciences, Tokyo Kasei University, Tokyo, Japan.
9
Centre for Microscopy and Microanalysis, The University of Queensland, St. Lucia, Queensland, Australia.
10
Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto, Japan.
11
National Institute of Chemistry, Ljubljana, Slovenia.
12
Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia; and.
13
Rikagaku Kenkyūsho (RIKEN), Saitama, Japan; toshihide.kobayashi@unistra.fr.
14
Unité Mixte de Recherche 7213, Centre National de la Recherche Scientifique, Université de Strasbourg, Illkirch, France.

Abstract

We identified a novel, nontoxic mushroom protein that specifically binds to a complex of sphingomyelin (SM), a major sphingolipid in mammalian cells, and cholesterol (Chol). The purified protein, termed nakanori, labeled cell surface domains in an SM- and Chol-dependent manner and decorated specific lipid domains that colocalized with inner leaflet small GTPase H-Ras, but not K-Ras. The use of nakanori as a lipid-domain-specific probe revealed altered distribution and dynamics of SM/Chol on the cell surface of Niemann-Pick type C fibroblasts, possibly explaining some of the disease phenotype. In addition, that nakanori treatment of epithelial cells after influenza virus infection potently inhibited virus release demonstrates the therapeutic value of targeting specific lipid domains for anti-viral treatment.-Makino, A., Abe, M., Ishitsuka, R., Murate, M., Kishimoto, T., Sakai, S., Hullin-Matsuda, F., Shimada, Y., Inaba, T., Miyatake, H., Tanaka, H., Kurahashi, A., Pack, C.-G., Kasai, R. S., Kubo, S., Schieber, N. L., Dohmae, N., Tochio, N., Hagiwara, K., Sasaki, Y., Aida, Y., Fujimori, F., Kigawa, T., Nishibori, K., Parton, R. G., Kusumi, A., Sako, Y., Anderluh, G., Yamashita, M., Kobayashi, T., Greimel, P., Kobayashi, T. A novel sphingomyelin/cholesterol domain-specific probe reveals the dynamics of the membrane domains during virus release and in Niemann-Pick type C.

KEYWORDS:

lipid binding protein; lipid raft; membrane lipids; sphingolipid

PMID:
27492925
DOI:
10.1096/fj.201500075R
[Indexed for MEDLINE]

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