在上皮细胞中发现了一种新的GREMLIN1吸收途径,该途径需要BMP结合
Zhichun Gao1, Yuhan Gao1, Louise R Dutton2
1Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast, Belfast, Northern Ireland, UK.
The Journal of biological chemistry
|October 1, 2025
概括
格雷姆林1 (GREM1) 蛋白由肠道细胞分泌,并被邻居吸收,需要骨形态遗传蛋白 (BMP) 结合以进行内部化,并可能调解BMP信号对抗.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 格雷姆林1 (GREM1) 通过在细胞外基质中结合BMPs来对抗骨形态遗传蛋白 (BMP) 信号传递.
- 目前尚不清楚GREM1与细胞表面受体的直接相互作用.
- 澄清GREM1的细胞机制对于理解其生物作用至关重要.
研究的目的:
- 阐明GREM1在肠道中的细胞吸收和信号传递机制.
- 研究BMP结合在GREM1内部化中的作用.
- 确定内部化GREM1.1的细胞定位和命运.
主要方法:
- 在肠道细胞中跟踪GREM1蛋白质的产生,分泌和内细胞分裂.
- 使用克拉特林和卡韦林介导的内细胞解路径.
- 在GREM1结合和吸收试验中使用酸蛋白糖.
- 产生和测试抗BMP的GREM1突变体.
主要成果:
- GREM1由肠道纤维细胞分泌,并由相邻的上皮细胞内细胞化.
- GREM1的吸收涉及克拉特林和卡韦林介导的内细胞分裂,取决于细胞表面的硫酸肝素蛋白质糖.
- 内化GREM1局限于早期内分泌体,可以重新分泌.
- BMP2增强了GREM1的吸收,而BMP结合对于GREM1的内部化至关重要.
结论:
- GREM1细胞吸收取决于BMP结合,这表明BMP信号对抗的新机制.
- 肝素硫酸盐蛋白质糖介导GREM1结合和内细胞化.
- GREM1的内化和再分泌代表了一种动态的细胞过程,影响BMP信号传递.
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