Separating planar cell polarity and Hippo pathway activities of the protocadherins Fat and Dachsous
Separating planar cell polarity and Hippo pathway activities of the protocadherins Fat and Dachsous
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DOI：
10.1242/dev.070367
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发表时间：
2012-04-15
期刊：
影响因子：
4.6
通讯作者：
Blair, Seth S.
中科院分区：
文献类型：
--
作者：
Matakatsu, Hitoshi;Blair, Seth S.
巨大的果蝇原钙粘蛋白脂肪（Ft）影响平面细胞极性（PCP）。Ft还通过Hippo途径抑制成虫盘的过度生长，抑制转录辅因子Yorkie（Yki）的活性。许多Ft活性可能由其胞内结构域（Ft ICD）介导。然而，人们对Ft ICD与五氯苯酚或Hippo活性之间的联系知之甚少，Hippo途径在五氯苯酚中的作用也不明确。我们对Ft ICD进行了结构-功能分析。我们发现Ft ICD对PCP和Hippo通路的影响在很大程度上是可分离的。令人惊讶的是，PCP和河马活动所需的结构域不映射到任何先前确定的蛋白质相互作用结构域，也没有，除了一个例外，在哺乳动物脂肪4中高度保守的区域。我们还发现，Ft的细胞外结构域可以独立于PCP中的Ft ICD发挥作用，并可能通过与原钙粘蛋白Dachsous结合，对Hippo活性产生显性负效应和边界效应。
The giant Drosophila protocadherin Fat (Ft) affects planar cell polarity (PCP). Ft also inhibits the overgrowth of imaginal discs via the Hippo pathway, repressing the activity of the transcription co-factor Yorkie (Yki). Much of Ft activity is likely to be mediated by its intracellular domain (Ft ICD). However, the links between the Ft ICD and either PCP or Hippo activity are poorly understood, and the role of the Hippo pathway in PCP is ambiguous. We have performed a structure-function analysis of the Ft ICD. We found that the effects of the Ft ICD on PCP and the Hippo pathway are largely separable. Surprisingly, the domains required for PCP and Hippo activities do not map to any of the previously identified protein interaction domains, nor, with one exception, to the regions that are highly conserved in mammalian Fat4. We also found that the extracellular domain of Ft can act independently of the Ft ICD in PCP and can trigger dominant-negative and boundary effects on Hippo activity, probably via binding to the protocadherin Dachsous.