细胞外载体控制了依赖脂质的 WNT 形态原体的分泌,输送和活性
Taciani de Almeida Magalhaes1, Jingjing Liu1, Charlene Chan1
1Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Developmental cell
|December 28, 2023
概括
分泌的蛋白质充当载体,从细胞中释放脂化WNT形态原体. 这些载体促进了WNT向受体的传递,并调节了WNT信号传递,影响了发展和再生医学.
科学领域:
- 细胞生物学 细胞生物学
- 发育生物学是发展生物学.
- 生物化学 生物化学
背景情况:
- WNT形态原体对于发育,再生和癌症至关重要.
- 用棕酸盐对WNT的脂化对于Frizzled (FZD) 受体结合和信号传递至关重要.
- 尽管依赖脂质的膜附着,但WNT从细胞释放和传播的机制仍然不清楚.
研究的目的:
- 阐明WNT形态原体从细胞中释放和传播的机制.
- 为了识别参与WNT分泌和细胞外运输的分子.
- 了解这些分子在WNT信号调节中的作用.
主要方法:
- 通过生物化学测定和基于细胞的实验,研究了WNT释放和运输.
- 鉴定出与FZD相关的分泌蛋白和WNT抑制因子1作为WNT载体.
- 描述了WNTLESS,载体,WNTs,glypicans,FZDs和NOTUM之间的相互作用.
主要成果:
- 分泌的FZD相关蛋白质和WNT抑制因子1作为脂化WNTs的强有力的载体.
- WNT释放涉及从膜蛋白WNTLESS直接传递给这些载体.
- 载体促进WNT转移到glypicans和FZD受体,以及到NOTUM酸酶进行非激活.
- 格利皮坎作为必要的共同受体,增强从载体到FZD的WNT转移.
结论:
- 载体的细胞外网络动态控制WNT形态基因分泌,后翻译修饰和输送.
- 这种机制为WNT信号调节提供了洞察力,并对再生医学有影响.
- 了解WNT载体功能是操纵WNT通路以获得治疗益处的关键.
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