Dynamic recruitment of axin by Dishevelled protein assemblies.
Dishevelled (Dvl) proteins are cytoplasmic components of the Wnt signalling pathway, which controls numerous cell fate decisions during animal development. During Wnt signalling, Dvl binds to the intracellular domain of the frizzled transmembrane receptors, and also to axin to block its activity, which results in the activation of beta-catenin and, consequently, in a transcriptional switch. We have previously reported that the DIX domain of mammalian Dvl2 allows it to form dynamic protein assemblies. Here, we show that these Dvl2 assemblies recruit axin, and also casein kinase Iepsilon. Using photobleaching experiments of GFP-tagged Dvl2 and axin to study the dynamics of their interaction, we found that the recruitment of axin-GFP by Dvl2 assemblies is accompanied by a striking acceleration of the dynamic properties of axin-GFP. We also show that the interaction between Dvl2 and axin remains highly dynamic even after Wnt-induced relocation to the plasma membrane. We discuss how the recruitment of casein kinase Iepsilon by Dvl2 assemblies might impact on the recruitment of axin to the plasma membrane during Wnt signalling.
Schwarz-Romond
Thomas
T
MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK.
Metcalfe
Ciara
C
Bienz
Mariann
M
D048868:Adaptor Proteins, Signal Transducing / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D060466:Axin Protein; D048149:Casein Kinase 1 epsilon / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism; D000072261:Dishevelled Proteins; D020868:Gene Silencing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000302:isolation & purification / Q000378:metabolism; D008840:Microfilament Proteins / Q000302:isolation & purification / Q000378:metabolism; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000302:isolation & purification / Q000378:metabolism; D012097:Repressor Proteins / Q000302:isolation & purification / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D014162:Transfection; D051153:Wnt Proteins / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; D057137:DAX-1 Orphan Nuclear Receptor; C513335:DIXDC1 protein, human; D004268:DNA-Binding Proteins; C000606581:DVL2 protein, human; D000072261:Dishevelled Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; C539965:NR0B1 protein, human; D010750:Phosphoproteins; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D051153:Wnt Proteins; D048149:Casein Kinase 1 epsilon