波利多姆/SVEP1与Tie1结合,并促进淋巴内皮细胞的迁移
Ryoko Sato-Nishiuchi1, Masamichi Doiguchi1, Nanami Morooka1,2
1Division of Matrixome Research and Application, Institute for Protein Research, Osaka University , Suita, Japan.
The Journal of cell biology
|June 20, 2023
概括
细胞外基质蛋白质Polydom直接与Tie1结合,促进淋巴血管的发育. 这种相互作用激活PI3K/Akt通路,这对淋巴内皮细胞迁移和生存至关重要.
科学领域:
- 发展生物学 发展生物学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 波利多姆是一种细胞外矩阵蛋白质,对淋巴血管发育至关重要.
- 由于淋巴血管重塑缺陷,多体缺陷导致围产死亡.
- 波利多姆的作用背后的精确分子机制仍然不清楚.
研究的目的:
- 阐明Polydom调节淋巴血管发育的分子机制.
- 为了确定Polydom在淋巴内皮细胞中的直接相互作用伙伴.
- 为了研究Polydom激活的信号通路.
主要方法:
- 同免疫沉测试以确定多种群结合蛋白.
- 使用淋巴内皮细胞 (LEC) 进行细胞迁移测定.
- 信号通路 (PI3K,ERK) 的药理抑制以及LEC迁移和Akt酸化的评估.
- 在LEC中对Foxo1局部化的分析.
主要成果:
- 波利多姆直接与孤儿受体Tie1.1结合.
- 多边体与Tie1的结合促进了Tie1依赖的LEC迁移.
- 多种体诱导的LEC迁移由PI3K/Akt信号通路介导,由增强的Akt酸化和Foxo1.1的核排斥证明.
- 抑制ERK通路并没有影响Polydom诱导的迁移.
结论:
- 波利多姆作为Tie1.1.的一个生理连接体.
- 聚多体结合Tie1激活PI3K/Akt路径,促进LEC迁移.
- 这种机制对于适当的淋巴血管发育和重塑至关重要.
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