Wnt4 inhibits beta-catenin/TCF signalling by redirecting beta-catenin to the cell membrane.
BACKGROUND
During embryonic development, beta-catenin is central both to the transcriptional activation of Wnt [wingless-type MMTV (murine-mammary-tumour virus) integration site family] target genes and as a mediator of cell-cell adhesion. Signals that regulate its levels and subcellular localization are critical. One mechanism of Wnt signalling results in stabilization of beta-catenin protein, which leads to its translocation into the nucleus, where it interacts with TCF (T-cell factor, HMG box) and activates transcription of target genes. Less well understood are mechanisms of Wnt signalling that do not involve beta-catenin stabilization and result in inhibition of beta-catenin-mediated transcription.


RESULTS
Here, we show that a member of the Wnt protein family, Wnt4 (Wnt, member 4), regulates the subcellular localization of beta-catenin, redirecting it to the cell membrane. Unique among Wnts, this action does not affect the stability of beta-catenin but does prohibit its involvement in TCF gene transactivation.


CONCLUSIONS
This novel mechanism suggests that Wnt4 acts as a switch between the two modes of beta-catenin function, transcriptional activation and cell-cell adhesion.
Bernard
Pascal
P
Human Molecular Genetics laboratory, Prince Henry's Institute of Medical Research, Monash Medical Centre, PO Box 5152, Clayton 3168, VIC, Australia.
Fleming
Alice
A
Lacombe
Arnaud
A
Harley
Vincent R
VR
Vilain
Eric
E
D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D002450:Cell Communication / Q000235:genetics; D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D021381:Protein Transport / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics*; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060528:Wnt4 Protein; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
C495267:CTNNB1 protein, mouse; D051820:TCF Transcription Factors; C555581:WNT4 protein, human; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse; D051176:beta Catenin