| 研究課題/領域番号 |
15F14385
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| 研究種目 |
特別研究員奨励費
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| 配分区分 | 補助金 |
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| 応募区分 | 外国 |
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| 研究分野 |
細胞生物学
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| 研究機関 | 国立研究開発法人国立循環器病研究センター |
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研究代表者 |
望月 直樹 国立研究開発法人国立循環器病研究センター, 研究所, 副所長 (30311426)
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| 研究分担者 |
PHNG LI-KUN 国立研究開発法人国立循環器病研究センター, 研究所, 外国人特別研究員
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| 研究期間 (年度) |
2015-04-24 – 2018-03-31
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| 研究課題ステータス |
交付 (2016年度)
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| 配分額 *注記 |
2,200千円 (直接経費: 2,200千円)
2016年度: 1,100千円 (直接経費: 1,100千円)
2015年度: 1,100千円 (直接経費: 1,100千円)
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| キーワード | angiogenesis / endothelial cell / actin / Marcks1 / zebrafish / 血管新生 / 細胞骨格 / ミオシン / アクチン |
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| 研究実績の概要 |
I identified Marcksl1, an actin-binding protein, as a molecular regulator of endothelial cell cortex during blood vessel morphogenesis in the zebrafish embryo. During lumen formation, Marcksl1 localization is enriched in the apical membrane. Overexpression of the protein perturbed cell cortex integrity so that 1) excessive blebs form at the apical membrane during lumen expansion and 2) ectopic blebs from at the basal membrane in perfused vessels that dissipate after inhibiting blood flow. In addition, endothelial cells with increased Marcksl1 expression are irregular in shape so that they are more dilated than wild type cells. These findings suggest that Marcksl1 regulates endothelial cell cortex dynamics and strength and that a robust cortex is required to resist haemodynamic forces and maintain blood vessel structure.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
We aimed at identification of molecules that regulate lumen formation during angiogenesis. Marcks1 functions has been identified in our experiments. It regulates actin-bundling during lumen formation. Marcks1 is also involved in the establishment of apico-basal polarity. Therefore, the purpose of our research has been achieved. Moreover, using various probes for visualizing vascular structure, we have been able to observe the thin fillopodia during the extension of endothelial cells.
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| 今後の研究の推進方策 |
To fully understand the function of Marcksl1 in blood vessel morphogenesis, it is important to study endothelial cell behavior in the absence of the protein. To this end, I have generated marcksl1a and marcksl1b double mutant zebrafish, which I will analyze for vascular phenotypes. In addition, I will determine how Marcksl1 regulates endothelial cell cortex by examining whether 1) its F-actin binding domain is required for its activity, 2) cortical tension is altered in endothelial cells with increased or decreased Marcksl1 expression and 3), it regulates the process of membrane bleb retraction.
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