CRM1- and Ran-independent nuclear export of beta-catenin.
BACKGROUND
Activation of the Wnt pathway induces beta-catenin to localize inside the nucleus, where it interacts with transcription factors such as TCF/LEF-1. Regulation of the pathway occurs through a beta-catenin-degrading complex based on Axin and the tumor suppressor APC. We have previously found that beta-catenin import occurs independently of nuclear import factors but is similar to the import of the transport factors themselves do. APC, which can shuttle in and out of the nucleus, has been proposed to be responsible for reexport of beta-catenin in a CRM1-dependent manner.


RESULTS
We have studied beta-catenin export in vivo and in semipermeabilized cells. beta-catenin contains three export sequences. Export is insensitive to leptomycin B, a specific inhibitor of the CRM1-mediated pathway. It does not require nuclear RanGTP, and it can be reconstituted in the absence of additional soluble factors; this is consistent with nondirectional translocation of beta-catenin. Further observations suggest that beta-catenin subcellular distribution in vivo may depend primarily on retention through interaction with other cellular components. Finally, we show evidence that reexport is required for degradation of nuclear beta-catenin and that nuclei lack Axin, an essential component of the degradation machinery.


CONCLUSIONS
beta-catenin is exported independently of the CRM1 pathway. We propose a model of free, nondirectional nuclear translocation for beta-catenin, its localization being regulated by retention in the nucleus and degradation in the cytoplasm.
Wiechens
N
N
Max-Planck-Institute for Developmental Biology, Department of Cell Biology, Tübingen D-72076, Germany.
Fagotto
F
F
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D024002:HMGB Proteins; D028884:Karyopherins; D009154:Mutation; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear; D017384:Sequence Deletion; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000378:metabolism; D014981:Xenopus; D029867:Xenopus Proteins; D051176:beta Catenin; D020931:ran GTP-Binding Protein / Q000378:metabolism*; D000097606:Exportin 1 Protein
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D024002:HMGB Proteins; D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D029867:Xenopus Proteins; D051176:beta Catenin; D020931:ran GTP-Binding Protein; D000097606:Exportin 1 Protein; C495266:CTNNB1 protein, Xenopus