Molecular separation of two signaling pathways for the receptor, Notch
Molecular separation of two signaling pathways for the receptor, Notch
复制标题
DOI：
10.1016/j.ydbio.2007.10.030
复制
发表时间：
2008-01-15
影响因子：
2.7
通讯作者：
Giniger, Edward
中科院分区：
文献类型：
--
作者：
Le Gall, Maude;De Mattel, Cordell;Giniger, Edward
Notch在发育过程中的细胞命运规范和形态发生的许多方面都是必需的，包括神经发生和轴突引导。我们在此提供了遗传学和生物化学证据，证明Notch通过“非经典”，即非Su（H）介导的信号通路指导果蝇的轴突生长和导向，其特征在于与接头蛋白Disabled和Trio（AN酪氨酸激酶的辅助因子）相关。我们发现，缺乏其典型效应子Su（H）的结合位点的Notch形式对于受体的细胞命运功能几乎是无活性的，但在轴突图案化中很大程度上或完全是活性的。相反，从Notch中删除残疾人的结合位点会损害其在轴突图案化中的作用，而不会干扰细胞命运控制。最后，我们通过免疫共沉淀显示Notch蛋白在体内与Disabled和Trio物理相关。总之，这些数据提供了一个替代Notch信号通路，介导有丝分裂后，受体的形态发生功能的证据。(C)2007爱思唯尔公司All rights reserved.
Notch is required for many aspects of cell fate specification and morphogenesis during development, including neurogenesis and axon guidance. We here provide genetic and biochemical evidence that Notch directs axon gowth and guidance in Drosophila via a "non-canonical", i.e. non-Su(H)-mediated, signaling pathway, characterized by association with the adaptor protein, Disabled, and Trio, an accessory factor of the AN tyrosine kinase. We find that forms of Notch lacking the binding sites for its canonical effector, Su(H), are nearly inactive for the cell fate function of the receptor, but largely or fully active in axon patterning. Conversely, deletion from Notch of the binding site for Disabled impairs its action in axon patterning without disturbing cell fate control. Finally, we show by co-immunoprecipitation that Notch protein is physically associated in vivo with both Disabled and Trio. Together, these data provide evidence for an alternate Notch signaling pathway that mediates a postmitotic, morphogenetic function of the receptor. (C) 2007 Elsevier Inc. All rights reserved.