在p120链蛋白和E-cadherin之间的动态和静态相互作用调节细胞-细胞粘附的稳定性
Noboru Ishiyama1, Seung-Hye Lee, Shuang Liu
1Division of Signaling Biology, Ontario Cancer Institute, ON, Canada.
Cell
|April 8, 2010
概括
p120 卡特宁 (p120) 结合E-卡德林.
科学领域:
- 细胞粘附 细胞粘附
- 分子生物学分子生物学
- 结构生物学是结构生物学.
背景情况:
- 卡德林-卡特宁复合体对于细胞-细胞粘附稳定性至关重要.
- 对于这种稳定性来说,p120素 (p120) 与素柔膜域 (JMD) 的关联至关重要.
- 了解这种相互作用是解读细胞过程的关键,例如突触发育.
研究的目的:
- 阐明p120与E-cadherin JMD结合的结构基础.
- 研究破坏这种相互作用对细胞粘附和神经元形态发生的功能后果.
- 了解p120如何通过不同的结合点调节cadherin的稳定性.
主要方法:
- 进行X射线晶体学以确定p120异型4A与E-cadherin JMD (核心) 结合的结构.
- 位点定向的突变发生改变p120结合位点,并评估对cadherin相互作用在体外和细胞中的影响.
- 核磁共振 (NMR) 谱学用于研究p120-JMD相互作用和动态.
- 细胞测试以评估p120突变在神经元树突脊柱形态发生过程中的作用.
主要成果:
- 晶体结构显示了p120中的模块化结合口袋,这些结合口袋与E-cadherin JMD (核心) 相辅相成.
- 特定的p120突变破坏了与E-cadherin和N-cadherin的结合,影响了细胞粘附.
- 这些突变允许在树状脊柱形态发生过程中区分N-cadherin依赖和N-cadherin独立的步骤.
- 核磁共振研究表明p120与JMD相关,影响内细胞和无位.
结论:
- 通过与JMD的特定相互作用,p120catenin稳定了由cadherin介导的细胞-细胞粘附.
- p120的结合点通过屏蔽参与内细胞分裂和无化的关键残留物来调节卡德林的稳定性.
- 扰乱p120-cadherin相互作用为突触发育的分子机制提供了洞察力.
相关概念视频
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