Abstract
Axin is a negative regulator of the Wnt pathway essential for down-regulation of beta-catenin. Axin has been considered so far as a cytoplasmic protein. Here we show that, although cytoplasmic at steady state, Axin shuttles in fact in and out of the nucleus; Axin accumulates in the nucleus of cells treated with leptomycin B, a specific inhibitor of the CRM1-mediated nuclear export pathway and is efficiently exported from Xenopus oocyte nuclei in a RanGTP- and CRM1-dependent manner. We have characterized the sequence requirement for export and identified two export domains, which do not contain classical nuclear export consensus sequences, and we show that Axin binds directly to the export factor CRM1 in the presence of RanGTP.
Highlights
Wnts constitute a large family of growth factors, conserved from invertebrates to humans, which are involved in many developmental processes, including early patterning events such as dorsoventral polarity of vertebrate embryos or segmentation of the Drosophila embryo [1, 2]
Cytoplasmic at steady state, Axin shuttles in and out of the nucleus; Axin accumulates in the nucleus of cells treated with leptomycin B, a specific inhibitor of the CRM1-mediated nuclear export pathway and is efficiently exported from Xenopus oocyte nuclei in a RanGTP- and CRM1-dependent manner
We have characterized the sequence requirement for export and identified two export domains, which do not contain classical nuclear export consensus sequences, and we show that Axin binds directly to the export factor CRM1 in the presence of RanGTP
Summary
Wnts constitute a large family of growth factors, conserved from invertebrates to humans, which are involved in many developmental processes, including early patterning events such as dorsoventral polarity of vertebrate embryos or segmentation of the Drosophila embryo [1, 2]. Cytoplasmic at steady state, Axin shuttles in and out of the nucleus; Axin accumulates in the nucleus of cells treated with leptomycin B, a specific inhibitor of the CRM1-mediated nuclear export pathway and is efficiently exported from Xenopus oocyte nuclei in a RanGTP- and CRM1-dependent manner.
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