Presenilin 1 interaction in the brain with a novel member of the Armadillo family
Presenilin 1 interaction in the brain with a novel member of the Armadillo family
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DOI：
10.1097/00001756-199705260-00054
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发表时间：
1997-05-27
期刊：
影响因子：
1.7
通讯作者：
Kosik, KS
中科院分区：
文献类型：
--
作者：
Zhou, JH;Liyanage, U;Kosik, KS
了解早老素1（PS1）功能的一种方法是发现与其相互作用的蛋白质。在发育模式中的功能的证据来自秀丽隐杆线虫，其中PS同源物是通过筛选Notch/lin-12（一种指定细胞命运的基因）中突变的抑制子来鉴定的。然而，这项遗传实验无法确定哪些蛋白质直接与PS1相互作用。因此，我们利用双杂交系统和确证性免疫共沉淀来鉴定一种新的连环蛋白，称为delta-catenin，它与PS1相互作用，主要在脑中表达。连环蛋白是与果蝇中的Armadillo基因相关的基因家族，其中一些似乎具有双重作用-它们是细胞-细胞粘附连接的组分，并且可能作为无翼（Wg）信号通路的中间体，其与Notch/lin-12一样，也负责各种诱导信号事件。在非神经元293细胞系中，PS1与β-连环蛋白相互作用，β-连环蛋白是与Armadillo具有最大同源性的家族成员。Wg和Notch相互作用由Dishevelled基因介导，该基因可与PS1和Wg途径中间体形成信号复合物以调节Notch/lin-12基因的功能。
ONE approach to understanding the function of presenilin 1 (PS1), is to discover those proteins with which it interacts. Evidence for a function in developmental patterning came from C, elegans, in which a PS homologue was identified by screening for suppressors of a mutation in Notch/lin-12, a gene which specifies cell fate. However, this genetic experiment cannot determine which proteins directly interact with PS1. Therefore, we utilized the two hybrid system and confirmatory co-immunoprecipitations to identify a novel catenin, termed delta-catenin, which interacts with PS1 and is principally expressed in brain. The catenins are a gene family related to the Armadillo gene in Drosophila, some of which appear to have dual roles - they are components of cell-cell adherens junctions, and may serve as intermediates in the Wingless (Wg) signaling pathway, which, like Notch/lin-12, is also responsible for a variety of inductive signaling events. In the non-neuronal 293 cell line, PS1 interacted with beta-catenin, the family member with the greatest homology to Armadillo. Wg and Notch interactions are mediated by the Dishevelled gene, which may form a signaling complex with PS1 and Wg pathway intermediates to regulate the function of the Notch/lin-12 gene.