Separating planar cell polarity and Hippo pathway activities of the protocadherins Fat and Dachsous

被引:69
|
作者
Matakatsu, Hitoshi [1 ]
Blair, Seth S. [1 ]
机构
[1] Univ Wisconsin Madison, Dept Zool, Madison, WI 53706 USA
来源
DEVELOPMENT | 2012年 / 139卷 / 08期
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
Fat; Fat4; Fat-J; Dachsous; PCP; Hippo; Warts; Lats; Yorkie; Expanded; Bantam; TUMOR-SUPPRESSOR PATHWAY; RECEPTOR TYROSINE KINASE; SIGNALING PATHWAY; DROSOPHILA EYE; REGULATE GROWTH; CADHERIN SUPERFAMILY; BANTAM MICRORNA; GENE; PROLIFERATION; SIZE;
D O I
10.1242/dev.070367
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
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页码:1498 / 1508
页数:11
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