Plasma membrane recruitment of dephosphorylated beta-catenin upon activation of the Wnt pathway.
The standard model of Wnt signaling specifies that after receipt of a Wnt ligand at the membranous receptor complex, downstream mediators inhibit a cytoplasmic destruction complex, allowing beta-catenin to accumulate in the cytosol and nucleus and co-activate Wnt target genes. Unexpectedly, shortly after Wnt treatment, we detected the dephosphorylated form of beta-catenin at the plasma membrane, where it displayed a discontinuous punctate labeling. This pool of beta-catenin could only be detected in E-cadherin(-/-) cells, because in E-cadherin(+/+) cells Wnt-induced, membranous beta-catenin was concealed by a constitutive junctional pool. Wnt-signaling-dependent dephosphorylated beta-catenin colocalized at the plasma membrane with two members of the destruction complex -- APC and axin -- and the activated Wnt co-receptor LRP6. beta-catenin induced through the Wnt receptor complex was significantly more competent transcriptionally than overexpressed beta-catenin, both in cultured cells and in early Xenopus embryos. Our data reveal a new step in the processing of the Wnt signal and suggest regulation of signaling output beyond the level of protein accumulation.
Hendriksen
Jolita
J
Department of Tumor Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Jansen
Marnix
M
Brown
Carolyn M
CM
van der Velde
Hella
H
van Ham
Marco
M
Galjart
Niels
N
Offerhaus
G Johan
GJ
Fagotto
Francois
F
Fornerod
Maarten
M
D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D000818:Animals; D060466:Axin Protein; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D046911:Macromolecular Substances / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D011973:Receptors, LDL / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology; D051153:Wnt Proteins / Q000378:metabolism*; D060508:Wnt3 Protein; D029867:Xenopus Proteins; D014982:Xenopus laevis; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D025601:Adenomatous Polyposis Coli Protein; D060466:Axin Protein; D015820:Cadherins; C555475:LRP6 protein, human; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C555476:Lrp6 protein, mouse; D046911:Macromolecular Substances; D011973:Receptors, LDL; D012097:Repressor Proteins; D051153:Wnt Proteins; D060508:Wnt3 Protein; D029867:Xenopus Proteins; C555454:axin1 protein, Xenopus; D051176:beta Catenin