Unexpectedly robust assembly of the Axin destruction complex regulates Wnt/Wg signaling in Drosophila as revealed by analysis in vivo.
Secreted proteins in the Wnt family regulate gene expression in target cells by causing the accumulation of the transcriptional activator beta-catenin. In the absence of Wnt, a protein complex assembled around the scaffold protein Axin targets beta-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 beta-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, AxinDeltaRGS and AxinDeltabeta cat(DeltaArm), 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.
Department of Cell and Developmental Biology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road/L215, Portland, OR 97239-3098, USA.
Wynne
W
Peterson-Nedry
Naz
N
Erdeniz
Susan
S
Kremer
Jessica
J
Yu
Shahana
S
Baig-Lewis
Marcel
M
Wehrli
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D060466:Axin Protein; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D017384:Sequence Deletion; D015398:Signal Transduction; D013816:Thermodynamics; D051153:Wnt Proteins / Q000378:metabolism*; D051155:Wnt1 Protein
D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; C118000:Axn protein, Drosophila; D029721:Drosophila Proteins; D050505:Mutant Proteins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D051155:Wnt1 Protein; C074622:wg protein, Drosophila