A novel sphingomyelin/cholesterol domain-specific probe reveals the dynamics of the membrane domains during virus release and in Niemann- Pick type C
A novel sphingomyelin/cholesterol domain-specific probe reveals the dynamics of the membrane domains during virus release and in Niemann- Pick type C
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DOI：
10.1096/fj.201500075r
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发表时间：
2017-04-01
期刊：
影响因子：
4.8
通讯作者：
Kobayashi, Toshihide
中科院分区：
文献类型：
--
作者：
Makino, Asami;Abe, Mitsuhiro;Kobayashi, Toshihide
我们发现了一种新型无毒蘑菇蛋白，它能特异性地与鞘磷脂（SM）（哺乳动物细胞中的主要鞘脂）和胆固醇（Chol）的复合物结合。纯化的蛋白质，被称为nakanori，标记细胞表面结构域中的SM和胆固醇依赖的方式和装饰特定的脂质结构域，共定位与内小叶小GT3-H-Ras，但不是K-Ras。使用nakanori作为脂质结构域特异性探针揭示了尼曼-匹克C型成纤维细胞表面SM/Chol的分布和动力学改变，这可能解释了一些疾病表型。此外，在流感病毒感染后对上皮细胞的nakanori治疗有效地抑制了病毒释放，证明了靶向特定脂质结构域用于抗病毒治疗的治疗价值。Makino，A.，阿贝，M.，石冢河，Murate，M.，Kishimoto，T.，Sakai，S.，Hullin-Matsuda，F.，Shimada，Y.，Inaba，T.，宫武，H.，Tanaka，H.，Kurahashi，A.，帕克，C.- G.，加塞河美国，Kubo，S.，Schieber，N. L.，Dohmae，N.，Tochio，N.，Hagiwara，K.，Sasaki，Y.，艾达，Y.，Fujimori，F.，Kigawa，T.，Nishibori，K.，帕顿河G.，Kusumi，A.，Sako，Y.，Anderluh，G.，Yamashita，M.，小林，格雷梅尔，P。，小林、T.一种新的鞘磷脂/胆固醇结构域特异性探针揭示了病毒释放过程中和尼曼-匹克C型中膜结构域的动力学。=
We identified a novel, nontoxicmushroomprotein 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. =