Single-Molecule Study of β-Catenin Translocation and the Role of Custos in its Regulation

Abstract

The nuclear pore complex is closely involved in the regulation and control of many cellular processes, including the movement of molecules into and out of the nucleus along with the regulation of gene transcription. It is therefore a major barrier for controlling the passage of signaling molecules into and out of the nucleus. β-catenin is one such signaling molecule, and a primary signaling molecule of the Wnt signaling pathway. How the passage of β-catenin into and out of the nucleus is controlled remains poorly defined. This signaling pathway governs major developmental processes, including cell fate determination, proliferation, motility and primary axis and head formation during development. In this study, we use super-resolution microscopy to show that β-catenin import requires Custos as a docking protein. Custos and β-catenin form a complex in the cytoplasm and move together through the NPC into the nucleus, where they dissociate in the nucleus. Further, we provide evidence that import of β-catenin into the nucleus is a regulatory event at the NPC and define regions within the β-catenin protein required for this regulation.