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Development and Application of Rapamycin-regulated Tyrosine Phosphatases
Published on: September 6, 2024
Dynamic changes in Rap1 activity are required for cell retraction and spreading during mitosis
Vi Thuy Dao1, Aurélien Guy Dupuy, Olivier Gavet
1Institut Curie, Centre de Recherche, Inserm U528, 26 rue d'Ulm, 75248 Paris, France.
Journal of Cell Science
|July 30, 2009
Summary
Rap1 GTPase activity regulates cell shape changes during mitosis. Inhibiting Rap1 prevents cell retraction before mitosis and spreading after, impacting cell division.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Adherent cells retract and round up at mitosis onset, disassembling focal adhesions and actin stress fibers.
- The small GTPase Rap1 is known to promote integrin-dependent cell adhesion and spreading.
Purpose of the Study:
- To investigate the role of Rap1 GTPase activity in regulating cell shape dynamics during mitosis.
- To determine how Rap1 activity changes during mitosis and its impact on cell adhesion processes.
Main Methods:
- Utilized HeLa cells to study Rap1 activity during the cell cycle.
- Manipulated Rap1 activity using endogenous regulation and ectopic expression of dominant-negative mutants (Rap1[S17A]).
- Monitored focal adhesion dynamics, actin cytoskeleton organization, and cell spreading post-mitosis.
Main Results:
- Endogenous Rap1 activity is inhibited at mitosis onset, correlating with cell retraction.
- Constitutive Rap1 activation prevents focal adhesion and actin cytoskeleton disassembly, delaying mitosis and causing cytokinesis defects.
- Increased Rap1 activity post-mitosis is crucial for cell spreading; its inhibition prevents spreading.
Conclusions:
- Rap1 GTPase activity is directly regulated during mitosis, controlling cell retraction and spreading.
- Rap1 plays a critical role in coordinating cell adhesion dynamics with the cell division cycle.
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