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DVL1 and DVL3 require nuclear localisation to regulate proliferation in human myoblasts
Johanna Pruller1, Nicolas Figeac1, Peter S Zammit2
1King's College London, Randall Centre for Cell and Molecular Biophysics, London, SE1 1UL, UK.
Scientific Reports
|May 19, 2022
Summary
Dishevelled (DVL) proteins DVL1 and DVL3 are crucial for human muscle stem cell proliferation and differentiation. Their nuclear presence regulates proliferation in both myoblasts and rhabdomyosarcoma, independent of canonical WNT signaling.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- WNT signaling regulates critical cellular processes, including skeletal muscle stem cell maintenance and differentiation.
- Dishevelled (DVL) proteins are key signal transducers in the WNT pathway, propagating signals from the cell membrane to the nucleus.
- Research often focuses on core WNT components like β-CATENIN, but the role of DVL proteins in myogenesis and related cancers is less understood.
Purpose of the Study:
- To investigate the function of Dishevelled (DVL) proteins in human myogenesis.
- To explore the role of DVL proteins in alveolar rhabdomyosarcoma, a muscle-related cancer.
- To elucidate the specific domains and nuclear localization requirements for DVL1 and DVL3 in proliferation control.
Main Methods:
- Studied DVL1 and DVL3 expression and function in human myoblasts.
- Analyzed the impact of DVL1 and DVL3 on myoblast proliferation and myogenic differentiation.
- Investigated DVL protein function and localization in alveolar rhabdomyosarcoma cells.
- Examined the necessity of specific DVL protein domains (DIX, PDZ) for proliferation regulation.
Main Results:
- DVL1 and DVL3 are essential for efficient proliferation of human myoblasts.
- These DVL proteins are important for timely myogenic differentiation.
- DVL1 and DVL3 contribute to the regulation of proliferation in rhabdomyosarcoma.
- Nuclear localization of DVL1 or DVL3 is required for proliferation control, with distinct domain requirements for each.
- DVL1 and DVL3 activity occurs independently of significant nuclear translocation of β-CATENIN.
Conclusions:
- DVL1 and DVL3 play critical, non-canonical roles in human myogenesis and rhabdomyosarcoma proliferation.
- The specific domains and nuclear function of DVL proteins are key to their roles in muscle development and cancer.
- Findings highlight DVL proteins as potential therapeutic targets in muscle-related cancers.
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