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First published online March 22, 2006
doi: 10.1242/10.1242/jcs.02864
Research Article |
Nikolaus-Fiebiger-Center for Molecular Medicine, University of Erlangen-Nürnberg, Glückstr. 6, 91054 Erlangen, Germany
* Author for correspondence (e-mail: jbehrens{at}molmed.uni-erlangen.de)
Accepted 19 December 2005
ß-catenin is the central signalling molecule of the canonical Wnt pathway, where it activates target genes in a complex with LEF/TCF transcription factors in the nucleus. The regulation of ß-catenin activity is thought to occur mainly on the level of protein degradation, but it has been suggested that ß-catenin nuclear localization and hence its transcriptional activity may additionally be regulated via nuclear import by TCF4 and BCL9 and via nuclear export by APC and axin. Using live-cell microscopy and fluorescence recovery after photobleaching (FRAP), we have directly analysed the impact of these factors on the subcellular localization of ß-catenin, its nucleo-cytoplasmic shuttling and its mobility within the nucleus and the cytoplasm. We show that TCF4 and BCL9/Pygopus recruit ß-catenin to the nucleus, and APC, axin and axin2 enrich ß-catenin in the cytoplasm. Importantly, however, none of these factors accelerates the nucleo-cytoplasmic shuttling of ß-catenin, i.e. increases the rate of ß-catenin nuclear import or export. Moreover, the cytoplasmic enrichment of ß-catenin by APC and axin is not abolished by inhibition of CRM-1-dependent nuclear export. TCF4, APC, axin and axin2 move more slowly than ß-catenin in their respective compartment, and concomitantly decrease ß-catenin mobility. Together, these data indicate that ß-catenin interaction partners mainly regulate ß-catenin subcellular localization by retaining it in the compartment in which they are localized, rather than by active transport into or out of the nucleus.
Key words: Wnt signalling, ß-Catenin, Nucleo-cytoplasmic shuttling, FRAP
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