Xenopus axin-related protein: A link between its centrosomal localization and function in the Wnt/β-catenin pathway

Abstract

The Wnt/β-catenin signaling pathway regulates cell proliferation and cell fate determination in multiple systems. However, the subcellular localization of Wnt pathway components and the significance of this localization for the pathway regulation have not been extensively analyzed. Here we report that Xenopus Axin-related protein (XARP), a component of the β-catenin destruction complex, is localized to the centrosome. This localization of XARP requires the presence of the DIX domain and an adjacent region. Since other components of the Wnt pathway have also been shown to associate with the centrosome, we tested a hypothesis that the β-catenin destruction complex operates at the centrosome. However, XARP mutants with poor centrosomal localization revealed an enhanced rather than decreased ability to antagonize the Wnt/β-catenin pathway. Our data are consistent with the idea that the inactivation of XARP at the centrosome is an important regulatory point in Wnt signaling. © 2009 Wiley-Liss, Inc.