Unexpectedly robust assembly of the Axin destruction complex regulates Wnt/Wg signaling in Drosophila as revealed by analysis in vivo

Wynne Peterson-Nedry, Naz Erdeniz, Susan Kremer, Jessica Yu, Shahana Baig-Lewis, Marcel Wehrli

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Secreted proteins in the Wnt family regulate gene expression in target cells by causing the accumulation of the transcriptional activator β-catenin. In the absence of Wnt, a protein complex assembled around the scaffold protein Axin targets β-catenin for destruction, thereby preventing it from transducing inappropriate signals. Loss of Axin or its binding partners APC and GSK3 results in aberrant activation of the Wnt signaling response. We have analyzed the effects of mutant forms of Drosophila Axin with large internal deletions when expressed at physiological levels in vivo, either in the presence or absence of wild type Axin. Surprisingly, even deletions that completely remove the binding sites for fly APC, GSK3 or β-catenin, though they fail to rescue to viability, these mutant forms of Axin cause only mild developmental defects, indicating largely retained Axin function. Furthermore, two lethal Axin deletion constructs, AxinΔRGS and AxinΔβcat(ΔArm), can complement each other and restore viability. Our findings support a model in which the Axin complex is assembled through cooperative tripartite interactions among the binding partners, making the assembly of functional complexes surprisingly robust.

Original languageEnglish (US)
Pages (from-to)226-241
Number of pages16
JournalDevelopmental Biology
Volume320
Issue number1
DOIs
StatePublished - Aug 1 2008

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Catenins
Wnt Proteins
Drosophila
Axin Protein
Diptera
Binding Sites
Gene Expression

Keywords

  • APC
  • Axin
  • beta-catenin
  • Complex assembly
  • Destruction complex
  • Drosophila
  • GSK3
  • In vivo
  • Mutant analysis
  • Scaffold
  • Wnt signaling

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Unexpectedly robust assembly of the Axin destruction complex regulates Wnt/Wg signaling in Drosophila as revealed by analysis in vivo. / Peterson-Nedry, Wynne; Erdeniz, Naz; Kremer, Susan; Yu, Jessica; Baig-Lewis, Shahana; Wehrli, Marcel.

In: Developmental Biology, Vol. 320, No. 1, 01.08.2008, p. 226-241.

Research output: Contribution to journalArticle

Peterson-Nedry, Wynne ; Erdeniz, Naz ; Kremer, Susan ; Yu, Jessica ; Baig-Lewis, Shahana ; Wehrli, Marcel. / Unexpectedly robust assembly of the Axin destruction complex regulates Wnt/Wg signaling in Drosophila as revealed by analysis in vivo. In: Developmental Biology. 2008 ; Vol. 320, No. 1. pp. 226-241.
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