CELL INTERACTIONS ORGANIZING THE INSECT SEGMENT

Hedgehog(HH)分泌蛋白家族介导了多种短小的- 果蝇发育过程中的靶细胞信号事件及几种 脊椎动物。这项研究的长期目标是了解 HH信号转导及其与其他细胞过程的整合。 Hb被认为是一种形态生成物，具有特定水平的HH 指定唯一响应的信号。这项工作的主要目标是 确定不同级别的HH信令如何定性地 不同的反应。最新的遗传和分子证据支持 Smoothens(Smo)的参与，可能是7个跨膜蛋白(7-TM) 受体，作为一种HH受体。这项拟议的研究使用了体内细胞 培养和生化方法探索Smo在HH中的作用 发信号。四个具体目标概述了该提案： 1)测试HH和Smo之间的物理相互作用， 2)检测异源三聚体G蛋白参与HH信号转导， 3)另一种细胞表面蛋白Patted对Smo的调节试验， 和 4)蛋白激酶A对Smo的调节作用。 这些实验将探索Smo在HH信号中的作用和调节 转导。由此产生的对SMO监管的描述可能会 7-TM受体介导的更广泛背景下的深刻含义 生理学和生物学。HH信号控制关键神经的产生 因小儿麻痹症和帕金森氏症等疾病而枯竭的人口。 了解HH信号可能会导致预防 失去或替换这些神经细胞群体。

The Hedgehog (Hh) family of secreted proteins mediates a variety of short- range cell signalling events in development of Drosophila and several vertebrates. The long term objectives of this research are to understand Hh signal transduction and its integration with other cellular processes. Hb has been proposed to act as a morphogen, with specific levels of Hh signal specifying unique responses. The principal goal of the work is to determine how different levels of Hh signaling lead to qualitatively different responses. Recent genetic and molecular evidence supports the involvement of Smoothened (Smo), a putative seven transmembrane (7-TM) receptor, as a Hh receptor. The proposed research uses in vivo, cell culture, and biochemical approaches to explore the role of Smo in Hh signaling. Four Specific Aims outline the proposal: 1) Test for physical interaction between Hh and Smo, 2) Test for participation of heterotrimeric G proteins in Hh signaling, 3) Test for regulation of Smo by Patched, another cell surface protein, and 4) Test for regulation of Smo by Protein Kinase A. These experiments will explore the role and regulation of Smo in Hh signal transduction. The resulting description of Smo regulation could have profound implications in the broader context of 7-TM receptor-mediated physiology and biology. Hh signaling controls the generation of key neural populations which are depleted in diseases such as polio and Parkinson's. Understanding Hh signaling could lead to strategies for preventing the loss of or for replacing these neural populations.