Different strategies by distinct Wnt-signaling pathways in activating a nuclear transcriptional response.

Abstract

The Wnt family of secreted glycolipo-proteins signals through multiple signal transduction pathways and is essential for embryonic development and organ development and homeostasis. The Wnt-pathways are conserved and critical in all metazoans. Wnt signaling pathways comprise the canonical Wnt/β-catenin pathway and several non-canonical signaling branches, of which Wnt-Planar Cell Polarity (PCP) signaling and the Wnt/Calcium pathway have received the most attention and are best understood. nterestingly, all Wnt-pathways have a nuclear signaling branch and also can affect many cellular processes independent of its nuclear transcriptional regulation. Canonical Wnt/β-catenin signaling is the most critical for a nuclear transcriptional response, in both development and disease, yet the mechanism(s) on how the "business end" of the pathway, β-catenin, translocates to the nucleus to act as co-activator to the TCF/Lef transcription factor family still remains obscure. Here we discuss and compare the very different strategies on how the respective Wnt signaling pathways activate a nuclear transcriptional response. We also highlight some recent new insights into how β-catenin is translocated to the nucleus via an IFT-A, Kinesin-2, and microtubule dependent mechanism and how this aspect of canonical Wnt-signaling uses ciliary proteins in a cilium independent manner, conserved between Drosophila and mammalian cells.