細胞の運動性と形状の操作による走化性シグナル伝達機構の制御と理解

通过操纵细胞运动和形状来控制和理解趋化信号传导机制

• 批准号: 14J09897
• 负责人: 福神 史仁
• 金额: $ 1.28万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2014
• 资助国家: 日本
• 起止时间: 2014-04-25 至 2016-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14J09897/
• 关键词: 細胞性粘菌; 細胞運動; アクチン; 微小流体デバイス

細胞性粘菌は，細胞外cAMPに依存したcAMPの合成と分泌(cAMPリレー応答)により大域的ならせん波様のcAMP濃度場を形成し(cAMP振動)，cAMPを誘引物質とする走化性運動により集合する．我々は，cAMPリレー応答等の細胞の応答が，細胞骨格タンパク質の量や，細胞の運動性や形状にどのように依存するかを検証した．アクチン重合阻害剤の濃度勾配下では，低濃度側でのcAMP振動の周期は短く，また低濃度側で多くのらせん波中心が生成されることがわかった．さらに，細胞と基質との間の接着を促進するポリマー分子を基質にコートした状況で集団のcAMP振動を観察することに成功し、その周期は増大することがわかった．この特徴は，野外環境においてアクチン重合の阻害等により運動しづらいような地点が存在したときに，そこからの距離が遠い地点に集合中心が生じやすくなる，という生存戦略を担っていると期待される．アクチン重合の薬理的阻害や基質接着の促進による細胞の重心移動の抑制により，F－アクチン量が減少することがわかった．cAMPリレー応答とF－アクチンの動態を同時可視化したところ，両応答の強度は正に相関することがわかった．また，細胞の形状の周期的変動と細胞内cAMP濃度の周期的変動の位相が一致する様子が時折観察された．以上の結果とこれまでの研究結果を合わせることで，一細胞レベルのcAMPリレー応答と細胞集団のcAMP振動は，F－アクチンや基質への接着に依存する現象である可能性が強く示唆された．細胞の応答の運動依存性が生物学的にも意義のある重要な特徴であることを示すことができた．細胞の挙動の理解をより深める上で，本研究のように，細胞の応答の運動依存性を解析することは重要であると考えられる．上記の結果とこれまでの研究結果に基づいた論文を投稿中である．

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