通过测量结合到未结合的Patched蛋白质的比率来读取刺形态梯度
1Howard Hughes Medical Institute, Department of Genetics and Development, Columbia University, New York, New York 10032, USA.
Nature
|August 10, 2004
概括
刺 (Hh) 信号依赖于补丁 (Ptc) 受体. 我们发现Hh结合的Ptc可以调节未结合的Ptc活动,揭示了细胞感知Hh度梯度的新机制.
科学领域:
- 发展生物学 发展生物学
- 细胞信号传递 细胞信号传递
- 分子生物学分子生物学
背景情况:
- 像 (Hh) 这样的形态原体通过形成度梯度来调节细胞发育.
- 补丁 (Ptc) 作为Hh受体,在没有Hh的情况下抑制Smo.
- 传统上,细胞对Hh的反应与活跃的,未结合的Ptc受体的数量有关.
研究的目的:
- 研究Hh结合Ptc在调节Hh信号中的作用.
- 为了确定Hh-bound Ptc是否影响Hh度梯度的解释.
- 探索形态原梯度传感的替代机制.
主要方法:
- 利用基因操纵来创造一种不能结合Hh.的Ptc形式.
- 评估了这种修改后的Ptc对Hh目标基因表达和渐变读数的影响.
- 量化了细胞反应中结合到未结合的Ptc的比例.
主要成果:
- Hh 结合的 Ptc 可以提升未结合的 Ptc 的抑制活性.
- 一个修改后的Ptc不能结合Hh,但保留了抑制功能,仍然允许正常的Hh梯度读数.
- 结合Hh与未结合Ptc的比例,而不仅仅是未结合Ptc的数量,决定了细胞的反应.
结论:
- 细胞对Hh度的感知受到绑定和未绑定Ptc之间的相互作用的影响.
- 这一发现挑战了只有活跃的,未结合的受体决定形态原度传感的模型.
- 一个修订后的模型表明,绑定/不绑定Ptc的比率对于准确的Hh梯度解释至关重要.
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