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Nuclear-enriched protein phosphatase 4 ensures outer kinetochore assembly prior to nuclear dissolution
Helder Rocha1,2, Patrícia A Simões1,2, Jacqueline Budrewicz3,4
1Instituto de Investigação e Inovação em Saúde - i3S, Universidade do Porto , Porto, Portugal.
The Journal of Cell Biology
|January 31, 2023
Summary
Protein phosphatase 4 (PP4) is crucial for outer kinetochore assembly before nuclear envelope breakdown (NEBD), ensuring proper chromosome-spindle engagement. Loss of PP4 causes chromosome mis-segregation, but recovery is possible via cytoplasmic factors.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Nuclear envelope breakdown (NEBD) is a key event in metazoan mitosis.
- Chromosome condensation and kinetochore assembly precede NEBD for spindle microtubule engagement.
Purpose of the Study:
- To investigate the role of nuclear-enriched protein phosphatase 4 (PP4) in outer kinetochore assembly before NEBD.
- To understand the consequences of PP4 deficiency on chromosome segregation and kinetochore function.
Main Methods:
- Studied PP4's role in kinetochore assembly using metazoan models.
- Assessed chromosome orientation and segregation following NEBD in PP4-deficient cells.
- Investigated the interaction between PP4 and CENP-C.
Main Results:
- PP4 ensures robust outer kinetochore assembly prior to NEBD.
- PP4 absence leads to monopolar chromosome orientation and mis-segregation post-NEBD.
- Cytoplasmic factors enable recovery of chromosome bi-orientation via the Ndc80-Ska module after NEBD.
Conclusions:
- PP4-dependent outer kinetochore assembly before NEBD is essential for accurate chromosome-spindle microtubule engagement.
- While PP4 is important, compensatory mechanisms exist for kinetochore assembly and chromosome recovery.
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