Dishevelled, a Wnt signalling component, is involved in mitotic progression in cooperation with Plk1
Koji Kikuchi1, Yohei Niikura, Katsumi Kitagawa
1Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan.
Abstract:
Wnt signalling is known to promote G1/S progression through the stimulation of gene expression, but whether this signalling regulates mitotic progression is not clear. Here, the function of dishevelled 2 (Dvl2), which transmits the Wnt signal, in mitosis was examined. Dvl2 localized to the spindles and spindle poles during mitosis. When cells were treated with nocodazole, Dvl2 was observed at the kinetochores (KTs). Dvl2 bound to and was phosphorylated at Thr206 by a mitotic kinase, Polo-like kinase 1 (Plk1), and this phosphorylation was required for spindle orientation and stable microtubule (MT)-KT attachment. Dvl2 was also found to be involved in the activation of a spindle assembly checkpoint (SAC) kinase, Mps1, and the recruitment of other SAC components, Bub1 and BubR1, to the KTs. However, the phosphorylation of Dvl2 by Plk1 was dispensable for SAC. Furthermore, Wnt receptors were involved in spindle orientation, but not in MT-KT attachment or SAC. These results suggested that Dvl2 is involved in mitotic progression by regulating the dynamics of MT plus-ends and the SAC in Plk1-dependent and -independent manners.
Insights
Dishevelled 2 (Dvl2) plays a key role in cell division by regulating spindle orientation and microtubule-kinetochore attachment during mitosis. This Wnt pathway protein is crucial for proper cell cycle progression.
Area of Science:
- Cell Biology
- Molecular Biology
- Signal Transduction
Background:
- Wnt signaling is known to regulate cell cycle progression at G1/S phase.
- Its role in mitotic progression remains unclear.
- Dishevelled 2 (Dvl2) is a key transducer of the Wnt signal.
Purpose of the Study:
- To investigate the function of Dishevelled 2 (Dvl2) during mitosis.
- To determine Dvl2's role in regulating mitotic progression and associated processes.
Main Methods:
- Immunofluorescence microscopy to localize Dvl2 during mitosis.
- Treatment with nocodazole to observe Dvl2 localization at kinetochores.
- Co-immunoprecipitation and in vitro kinase assays to study Dvl2 phosphorylation by Plk1.
- Analysis of spindle assembly checkpoint (SAC) components and spindle orientation.
Main Results:
- Dvl2 localizes to spindles, spindle poles, and kinetochores during mitosis.
- Dvl2 is phosphorylated by Polo-like kinase 1 (Plk1) at Thr206, which is essential for spindle orientation and microtubule-kinetochore attachment.
- Dvl2 contributes to spindle assembly checkpoint (SAC) activation and the recruitment of SAC proteins (Bub1, BubR1) to kinetochores.
- Plk1-dependent phosphorylation of Dvl2 is not required for SAC function.
- Wnt receptors influence spindle orientation but not kinetochore-microtubule attachment or SAC.
Conclusions:
- Dvl2 plays a critical role in mitotic progression.
- Dvl2 regulates microtubule dynamics and the SAC through Plk1-dependent and -independent mechanisms.
- These findings reveal a novel role for Wnt signaling components in mitosis.
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