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Phase separation of EB1 guides microtubule plus-end dynamics
Xiaoyu Song1,2, Fengrui Yang1,2, Tongtong Yang1
1MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, Hefei National Center for Cross-disciplinary Sciences, University of Science & Technology of China School of Life Sciences, Hefei, China.
Nature Cell Biology
|December 19, 2022
Summary
End-binding (EB) proteins form dynamic liquid condensates via liquid-liquid phase separation (LLPS) at microtubule plus-ends. This EB1 phase separation is crucial for microtubule dynamics and mitotic chromosome movement.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- End-binding (EB) proteins regulate microtubule dynamics and are vital for cellular functions.
- The precise molecular mechanisms governing EB protein interactions and their role in microtubule organization are not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms and physiochemical properties of the EB1 interaction network.
- To investigate the role of liquid-liquid phase separation (LLPS) in the function of EB1 at microtubule plus-ends.
Main Methods:
- In vitro characterization of EB1 phase separation.
- Live-cell imaging of chromosome segregation in HeLa cells expressing EB1 mutants.
- Biochemical analysis of EB1 multivalent interactions.
Main Results:
- EB1 proteins self-assemble into liquid condensates through LLPS, forming the microtubule plus-end machinery.
- Multivalent interactions, modulated by charged residues in the EB1 linker region, drive EB1 LLPS.
- Phase-separated EB1 concentrates tubulin dimers and other plus-end tracking proteins, influencing microtubule dynamics.
- EB1 LLPS is essential for proper mitotic chromosome segregation.
Conclusions:
- EB1 utilizes LLPS to form a distinct membraneless organelle at microtubule plus-ends.
- This EB1-driven condensate physically and biochemically organizes the microtubule plus-end machinery.
- EB1 LLPS is a critical regulator of microtubule dynamics and chromosome segregation during mitosis.
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