Sotillos S, Roch F, Campuzano S
Centro de Biología Molecular Severo Ochoa, CSIC and UAM, Madrid, Spain.
Development. 1997 Dec;124(23):4769-79. doi: 10.1242/dev.124.23.4769.
The Notch transmembrane protein is the receptor of an evolutionary conserved pathway that mediates intercellular signalling leading to the specification of different cell types during development. In this pathway, many aspects of the signal transduction mechanism remain poorly understood, especially the role of proteolytic processing of Notch. We present genetic evidence indicating that the metalloprotease-disintegrin kuzbanian (J. Rooke, D. Pan, T. Xu and G. M. Rubin (1996) Science 273, 1227-1231) is a new component of the Notch signalling pathway and is involved in Notch activation. kuzbanian genetic mosaics demonstrate that, during neurogenesis, wing margin formation and vein width specification kuzbanian is autonomously required in the cell where Notch is activated. Genetic interactions between kuzbanian and different genes of the Notch pathway indicate that kuzbanian is required upstream of Suppressor of Hairless. Moreover, the requirement of kuzbanian for signalling by a ligand-dependent Abruptex receptor, but not by a constitutively activated form of Notch, suggests that kuzbanian is involved in the generation of a Notch functional receptor and/or in its activation. However, differences in the phenotypes of loss-of-function Notch and kuzbanian mutations suggest the existence of alternative Kuzbanian-independent mechanisms that generate Notch functional receptors.
Notch跨膜蛋白是一种进化保守信号通路的受体，该信号通路介导细胞间信号传导，从而在发育过程中决定不同细胞类型的命运。在这条信号通路中，信号转导机制的许多方面仍知之甚少，尤其是Notch蛋白水解加工的作用。我们提供的遗传学证据表明，金属蛋白酶-解整合素库兹班（J. 鲁克、D. 潘、T. 徐和G. M. 鲁宾（1996年）《科学》273卷，1227 - 1231页）是Notch信号通路的一个新组分，并且参与Notch的激活。库兹班基因镶嵌体表明，在神经发生、翅缘形成和翅脉宽度决定过程中，在激活Notch的细胞中自主需要库兹班。库兹班与Notch信号通路不同基因之间的遗传相互作用表明，库兹班在无翅抑制因子上游发挥作用。此外，库兹班对于依赖配体的异常受体信号传导是必需的，但对于组成型激活形式Notch的信号传导则不是必需的，这表明库兹班参与Notch功能受体的产生和/或其激活。然而，功能丧失型Notch和库兹班突变表型的差异表明，存在不依赖库兹班的其他机制来产生Notch功能受体。
