酸化诱导的SUMOylation促进Ulk4凝聚在状尖端,以转换子信号
Mengmeng Zhou1, Yuhong Han1, Jin Jiang1,2
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
bioRxiv : the preprint server for biology
|November 28, 2024
概括
两个激酶,Stk36和Ulk4,通过酸化和SUMOylation控制Gli2蛋白在主要尖的定位和激活来调节子 (Hh) 途径. 这一过程形成了对Hh信号转导至关重要的生物分子凝聚物.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 发展生物学 发展生物学
背景情况:
- 刺 (Hh) 信号对胚胎发育和组织平衡至关重要.
- 转录因子的Gli家族介导Hh信号转导.
- 在脊椎动物中,Hh信号依赖于主要的纤毛,但纤毛尖上的Gli激活机制尚不清楚.
研究的目的:
- 为了阐明Gli2激活在初级尖的机制.
- 为了识别主要的调节者 Hh信号传导在初级纤毛.
- 调查Unc-51类激酶 (Ulk) 家族成员在Hh通路激活中的作用.
主要方法:
- 研究了 Stk36 和 Ulk4 在 Hh 信号传递中的作用.
- 使用生物化学分析来研究蛋白质酸化和SUMOylation.
- 检查了蛋白质-蛋白质相互作用和生物分子凝结物形成.
- 使用仿突变和SUMOylation缺陷突变来评估蛋白质功能.
- 分析了Gli2的定位和激活在主要尖上的情况.
主要成果:
- Stk36可化Ulk4,促进其SUMOylation作为对Shh.的反应.
- Ulk4的SUMOylation促进其与SUMO交互动机 (SIM) 的相互作用,驱动自组装成生物分子凝聚物.
- 这些凝结物招募Stk36和Gli2,导致Gli2在状尖端积累和激活.
- 在Ulk4 SUMOylation或SIM中存在的缺陷,会阻止尖的定位和Gli2的激活.
- 模仿性Ulk4突变诱导构成凝聚物形成和Shh通路激活.
结论:
- Ulk4的酸化依赖的SUMOylation是Hh信号转导的关键机制.
- Ulk4 SUMOylation促进了酶-基质凝聚在主要尖.
- 这一过程调节了Gli2活动,并调解了Shh信号通路.
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