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The conserved AAA-ATPase PCH-2 TRIP13 regulates spindle checkpoint strength
Lénaïg Défachelles1, Anna E Russo1, Christian R Nelson1
1Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064.
Molecular Biology of the Cell
|July 23, 2020
Summary
The AAA-ATPase PCH-2/TRIP13 regulates spindle checkpoint strength in Caenorhabditis elegans by controlling Mad2 conformation. Its requirement depends on cell volume and cell fate, particularly in germline precursor cells.
Area of Science:
- Cell Biology
- Genetics
- Developmental Biology
Background:
- The spindle checkpoint ensures accurate chromosome segregation during cell division.
- Checkpoint strength is influenced by factors including cell size and cell type.
- The AAA-ATPase PCH-2/TRIP13 is known to remodel the checkpoint effector Mad2.
Purpose of the Study:
- To investigate the role of PCH-2/TRIP13 in controlling spindle checkpoint strength.
- To determine how cell volume and cell fate affect PCH-2/TRIP13's function.
- To identify factors regulating PCH-2/TRIP13 activity and localization.
Main Methods:
- Genetic manipulation of cell volume in Caenorhabditis elegans.
- Analysis of spindle checkpoint activity and kinetochore-microtubule attachments.
- Immunofluorescence to assess Mad2 and PCH-2 localization.
- Investigating the role of CMT-1 (p31comet ortholog) in PCH-2 function.
Main Results:
- PCH-2/TRIP13 is essential for spindle checkpoint strength, particularly in larger cells and germline precursor cells.
- Reducing cell volume diminishes the requirement for PCH-2/TRIP13 in checkpoint function and Mad2 recruitment.
- PCH-2/TRIP13 enrichment in germline precursor cells depends on conserved asymmetry factors.
- CMT-1 regulates PCH-2 localization and enrichment, impacting checkpoint strength.
Conclusions:
- PCH-2/TRIP13 governs spindle checkpoint strength by modulating inactive Mad2 availability at kinetochores.
- The requirement for PCH-2/TRIP13 is adaptable, influenced by cell size and developmental context.
- These findings are relevant for understanding cell division in oocytes, early embryos, and germline cells.
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