title: A novel sphingomyelin/cholesterol domain-specific probe reveals the dynamics of the membrane domains during virus release and in Niemann-Pick type C.
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.
authors: Rikagaku Kenkyūsho (RIKEN), Saitama, Japan.
authors: Asami
authors: A
authors: Makino
authors: Rikagaku Kenkyūsho (RIKEN), Saitama, Japan.
authors: Mitsuhiro
authors: M
authors: Abe
authors: Rikagaku Kenkyūsho (RIKEN), Saitama, Japan.
authors: Reiko
authors: R
authors: Ishitsuka
authors: Rikagaku Kenkyūsho (RIKEN), Saitama, Japan.
authors: Motohide
authors: M
authors: Murate
authors: Rikagaku Kenkyūsho (RIKEN), Saitama, Japan.
authors: Takuma
authors: T
authors: Kishimoto
authors: Rikagaku Kenkyūsho (RIKEN), Saitama, Japan.
authors: Shota
authors: S
authors: Sakai
authors: Rikagaku Kenkyūsho (RIKEN), Saitama, Japan.|Université Lyon 1, INSERM, Unité 1060, Villeurbanne, France.
authors: Françoise
authors: F
authors: Hullin-Matsuda
authors: Rikagaku Kenkyūsho (RIKEN), Saitama, Japan.
authors: Yukiko
authors: Y
authors: Shimada
authors: Rikagaku Kenkyūsho (RIKEN), Saitama, Japan.
authors: Takehiko
authors: T
authors: Inaba
authors: Rikagaku Kenkyūsho (RIKEN), Saitama, Japan.
authors: Hideyuki
authors: H
authors: Miyatake
authors: Faculty of Core Research, Natural Science Division, Ochanomizu University, Tokyo, Japan.
authors: Hideko
authors: H
authors: Tanaka
authors: Yukiguni Maitake Co., Limited, Niigata, Japan.
authors: Atsushi
authors: A
authors: Kurahashi
authors: Rikagaku Kenkyūsho (RIKEN), Saitama, Japan.
authors: Chan-Gi
authors: CG
authors: Pack
authors: Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
authors: Rinshi S
authors: RS
authors: Kasai
authors: Daiichi Sankyo Co., Limited, Tokyo, Japan.
authors: Shuku
authors: S
authors: Kubo
authors: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia.
authors: Nicole L
authors: NL
authors: Schieber
authors: Rikagaku Kenkyūsho (RIKEN), Saitama, Japan.
authors: Naoshi
authors: N
authors: Dohmae
authors: Rikagaku Kenkyūsho (RIKEN), Saitama, Japan.
authors: Naoya
authors: N
authors: Tochio
authors: Rikagaku Kenkyūsho (RIKEN), Saitama, Japan.
authors: Kyoji
authors: K
authors: Hagiwara
authors: Rikagaku Kenkyūsho (RIKEN), Saitama, Japan.
authors: Yutaka
authors: Y
authors: Sasaki
authors: Rikagaku Kenkyūsho (RIKEN), Saitama, Japan.
authors: Yoko
authors: Y
authors: Aida
authors: Graduate School of Humanities and Life Sciences, Tokyo Kasei University, Tokyo, Japan.
authors: Fumihiro
authors: F
authors: Fujimori
authors: Rikagaku Kenkyūsho (RIKEN), Saitama, Japan.
authors: Takanori
authors: T
authors: Kigawa
authors: Yukiguni Maitake Co., Limited, Niigata, Japan.
authors: Kozo
authors: K
authors: Nishibori
authors: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia.|Centre for Microscopy and Microanalysis, The University of Queensland, St. Lucia, Queensland, Australia.
authors: Robert G
authors: RG
authors: Parton
authors: Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.|Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto, Japan.
authors: Akihiro
authors: A
authors: Kusumi
authors: Rikagaku Kenkyūsho (RIKEN), Saitama, Japan.
authors: Yasushi
authors: Y
authors: Sako
authors: National Institute of Chemistry, Ljubljana, Slovenia.|Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia; and.
authors: Gregor
authors: G
authors: Anderluh
authors: Daiichi Sankyo Co., Limited, Tokyo, Japan.
authors: Makoto
authors: M
authors: Yamashita
authors: Faculty of Core Research, Natural Science Division, Ochanomizu University, Tokyo, Japan.
authors: Tetsuyuki
authors: T
authors: Kobayashi
authors: Rikagaku Kenkyūsho (RIKEN), Saitama, Japan.
authors: Peter
authors: P
authors: Greimel
authors: Rikagaku Kenkyūsho (RIKEN), Saitama, Japan; toshihide.kobayashi@unistra.fr.|Unité Mixte de Recherche 7213, Centre National de la Recherche Scientifique, Université de Strasbourg, Illkirch, France.
authors: Toshihide
authors: T
authors: Kobayashi
mesh_terms: D001665:Binding Sites; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D048691:Grifola / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D021962:Membrane Microdomains / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D052556:Niemann-Pick Disease, Type C / Q000378:metabolism*; D011485:Protein Binding; D013109:Sphingomyelins / Q000378:metabolism*; D057074:Virus Release
chemical_list: D005656:Fungal Proteins; D013109:Sphingomyelins; D002784:Cholesterol
keywords: lipid binding protein; lipid raft; membrane lipids; sphingolipid