Wnt signaling recruits KIF2A to the spindle to ensure chromosome congression and alignment during mitosis
Anja Bufe1, Ana García Del Arco1, Magdalena Hennecke2
1Centre for Organismal Studies, Heidelberg University, D-69120 Heidelberg, Germany.
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. 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 cell division. We show that Wnt signaling modulates KIF2A interaction with PLK1, which is critical for KIF2A localization at the spindle. Accordingly, inhibition of basal Wnt signaling leads to chromosome misalignment in somatic cells and pluripotent stem cells. We propose that Wnt signaling monitors KIF2A activity at the spindle poles during mitosis to ensure timely chromosome alignment. Our findings highlight a function of Wnt signaling during cell division, which could have important implications for genome maintenance, notably in stem cells.
Insights
Wnt signaling regulates microtubule dynamics during mitosis by controlling KIF2A, ensuring proper chromosome alignment. This mitotic Wnt pathway is crucial for genome stability, particularly in stem cells.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- Canonical Wnt signaling regulates gene expression via β-catenin.
- Emerging evidence implicates β-catenin-independent Wnt signaling in mitosis.
- The specific targets and roles of mitotic Wnt signaling remain largely unknown.
Purpose of the Study:
- To identify targets of mitotic Wnt signaling.
- To characterize the function of mitotic Wnt signaling in mitosis.
- To investigate the role of Wnt signaling in chromosome alignment.
Main Methods:
- Phosphoproteomics to identify Wnt signaling targets.
- Dishevelled and KIF2A interaction studies.
- Analysis of KIF2A localization and function.
- Assessment of chromosome alignment upon Wnt signaling inhibition.
Main Results:
- Wnt signaling regulates the microtubule depolymerase KIF2A during mitosis.
- Dishevelled recruits KIF2A, a process enhanced by LRP6 signalosome formation.
- Wnt signaling modulates KIF2A interaction with PLK1, essential for spindle localization.
- Inhibition of Wnt signaling causes chromosome misalignment in somatic and pluripotent stem cells.
Conclusions:
- Wnt signaling monitors KIF2A activity at spindle poles to ensure timely chromosome alignment during mitosis.
- Mitotic Wnt signaling plays a vital role in genome maintenance, especially in stem cells.
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