The Drosophila tankyrase regulates Wg signaling depending on the concentration of Daxin.
The canonical Wnt signaling pathway plays critical roles during development and homeostasis. Dysregulation of this pathway can lead to many human diseases, including cancers. A key process in this pathway consists of regulation of β-catenin concentration through an Axin-recruited destruction complex. Previous studies have demonstrated a role for tankyrase (TNKS), a protein with poly(ADP-ribose) polymerase, in the regulation of Axin levels in human cells. However, the role of TNKS in development is still unclear. Here, we have generated a Drosophila tankyrase (DTNKS) mutant and provided compelling evidence that DTNKS is involved in the degradation of Drosophila Axin (Daxin). We show that Daxin physically interacts with DTNKS, and its protein levels are elevated in the absence of DTNKS in the eye discs. In S2 cells, DTNKS suppressed the levels of Daxin. Surprisingly, we found that Daxin in turn down-regulated DTNKS protein level. In vivo study showed that DTNKS regulated Wg signaling and wing patterning at a high Daxin protein level, but not at a normal level. Taken together, our findings identified a conserved role of DTNKS in regulating Daxin levels, and thereby Wg/Wnt signaling during development.
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China; School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Ying
Y
Feng
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
Xue
X
Li
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Lorraine
L
Ray
Laboratory of Food Safety, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, CAS, Shanghai 200031, China.
Haiyun
H
Song
School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Jia
J
Qu
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China. Electronic address: linsy@xmu.edu.cn.
Shuyong
S
Lin
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA. Electronic address: xinhua.lin@ioz.ac.cn.
Xinhua
X
Lin
D000818:Animals; D030801:Animals, Genetically Modified; D060466:Axin Protein / Q000378:metabolism*; D015536:Down-Regulation; D004330:Drosophila / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering; D038501:Tankyrases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014921:Wings, Animal / Q000033:anatomy & histology; D060449:Wnt Signaling Pathway
D060466:Axin Protein; C118000:Axn protein, Drosophila; D029721:Drosophila Proteins; D034741:RNA, Small Interfering; D038501:Tankyrases
Daxin; Drosophila; Tankyrase; Wg signaling