Wnt signaling recruits KIF2A to the spindle to ensure chromosome congression during mitosis

ABSTRACT: Canonical Wnt signaling plays critical roles in development and tissue renewal by regulating β-catenin target genes. Recent evidence showed that β-catenin-independent Wnt signaling is also required for faithful execution of mitosis. This mitotic Wnt signaling functions through Wnt-dependent stabilization of proteins (Wnt/STOP), as well as through components of the LRP6 signalosome. However, the targets and specific functions of mitotic Wnt signaling still remain uncharacterized. Using phosphoproteomics, we identified that Wnt signaling regulates the microtubule depolymerase KIF2A during mitosis. We found that Dishevelled recruits KIF2A via its N-terminal and motor domains, which is further promoted upon LRP6 signalosome formation during mitosis. We show that Wnt signaling modulates KIF2A interaction with PLK1, which is critical for KIF2A localization and the assembly of a bipolar mitotic spindle. Accordingly, Wnt signaling promotes chromosome congression during metaphase by monitoring KIF2A protein levels at the spindle poles both in somatic cells and in pluripotent stem cells. Our findings highlight a novel function of Wnt signaling during cell division, which could have important implications for genome maintenance, notably in stem cells.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Retinal Cell, Epithelial Cell

SUBMITTER: Petra Beli  

LAB HEAD: Petra Beli

PROVIDER: PXD022724 | Pride | 2021-11-17

REPOSITORIES: Pride