TY - JOUR
AU - Gleeson, Joseph G.
AB - Mechanisms of signal transduction regulation remain a fundamental question in a variety of biological processes and diseases. Previous evidence suggests the primary cilium can act as a signaling hub1, but its exact role in many of its described pathways has remained elusive. Here, we investigate the mechanism of cilia regulation of the canonical Wnt pathway through systematic knock-down and knock-out approaches. We found that the primary cilium dampens canonical Wnt signaling through a unique spatial mechanism involving compartmentalization of signaling components. The cilium, through regulated intraflagellar transport (IFT), diverts Jouberin (Jbn), a ciliopathy protein and context specific Wnt pathway regulator2, away from the nucleus and limits β-catenin nuclear entry. This repressive regulation does not silence the pathway, but instead maintains a discrete range of Wnt responsiveness; cells without cilia have potentiated Wnt responses whereas cells with more than one cilium display inhibited responses. Furthermore, we show that this regulation occurs during embryonic development and is disrupted in cancer cell proliferation. Together these data explain a unique spatial mechanism of regulation of Wnt signaling which may provide insight into ciliary regulation of other signaling pathways.
TI - Subcellular Spatial Regulation of Canonical Wnt Signaling at the Primary Cilium
JF - Nature cell biology
DO - 10.1038/ncb2259
DA - 2011-05-22
UR - https://www.deepdyve.com/lp/pubmed-central/subcellular-spatial-regulation-of-canonical-wnt-signaling-at-the-HlBZnWsnEn
SP - 700
EP - 707
VL - 13
IS - 6
DP - DeepDyve
ER -