九州大学-研究者情報 [木下祥尚 (助教) 理学研究院化学部門]

Masanao Kinoshita, Kenichi G. N. Suzuki, Nobuaki Matsumori, Misa Takada, Hikaru Ano, Kenichi Morigaki, Mitsuhiro Abe, Asami Makino, Toshihide Kobayashi, Koichiro M. Hirosawa, Takahiro K. Fujiwara, Akihiro Kusumi, Michio Murata, Raft-based sphingomyelin interactions revealed by new fluorescent sphingomyelin analogs, JOURNAL OF CELL BIOLOGY, 10.1083/jcb.201607086, 216, 4, 1183-1204, 2017.04, Sphingomyelin (SM) has been proposed to form cholesterol-dependent raft domains and sphingolipid domains in the plasma membrane (PM). How SM contributes to the formation and function of these domains remains unknown, primarily because of the scarcity of suitable fluorescent SM analogs. We developed new fluorescent SM analogs by conjugating a hydrophilic fluorophore to the SM choline headgroup without eliminating its positive charge, via a hydrophilic nonaethylene glycol linker. The new analogs behaved similarly to the native SM in terms of their partitioning behaviors in artificial liquid order-disorder phase-separated membranes and detergent-resistant PM preparations. Single fluorescent molecule tracking in the live-cell PM revealed that they indirectly interact with each other in cholesterol-and sphingosine backbone-dependent manners, and that, for similar to 10-50 ms, they undergo transient colocalization-codiffusion with a glycosylphosphatidylinositol (GPI)-anchored protein, CD59 (in monomers, transient-dimer rafts, and clusters), in CD59-oligomer size-, cholesterol-, and GPI anchoring-dependent manners. These results suggest that SM continually and rapidly exchanges between CD59-associated raft domains and the bulk PM..

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研究資金

科学研究費補助金の採択状況(文部科学省、日本学術振興会)

2017年度～2019年度, 若手研究(B), 電子線ナノ散乱法の開発と脂質ラフトの構造解明.

2018年度～2018年度, 特定奨励費, 代表, 膜貫通タンパク質の脂質ラフトへの取り込みと機能発現の相関.

2020年度～2022年度, 基盤研究(C), 脂質ラフトをターゲトとする新たな局所麻酔薬の作用機構の提唱.

2023年度～2025年度, 基盤研究(C), 代表, 脂質ラフトに対する膜タンパク質取り込みの機序とシャペロン仮説の実証.

競争的資金(受託研究を含む)の採択状況

2023年度～2023年度, 2023年度物質・デバイス領域共同研究拠点共同研究課題, 代表, 機能性分子としての適用を指向した生体膜に対するトリプチセン誘
導体の作用解析.