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A role for Cdc42 in macrophage chemotaxis
W E Allen1, D Zicha, A J Ridley
1Muscle and Motility Research Centre, Randall Institute, King's College London WC2B 5RL, UK.
The Journal of Cell Biology
|June 12, 1998
Summary
Rho and Rac proteins are essential for macrophage migration, while Cdc42 directs cells towards colony-stimulating factor-1 (CSF-1) gradients. This research clarifies the distinct roles of Rho family GTPases in directed cell movement.
Area of Science:
- Cell Biology
- Molecular Biology
- Cytoskeletal Dynamics
Background:
- Rho family GTPases (Rho, Rac, Cdc42) regulate actin cytoskeleton organization.
- Previous work established Rho's role in macrophage contraction and Rac/Cdc42 in lamellipodia/filopodia formation.
Purpose of the Study:
- To investigate the roles of Cdc42, Rac, and Rho in colony-stimulating factor-1 (CSF-1)-induced macrophage migration and chemotaxis.
- To elucidate the specific functions of these GTPases in directed cell movement.
Main Methods:
- Utilized the Dunn chemotaxis chamber for migration assays.
- Employed microinjection techniques with constitutively activated GTPases and dominant-negative mutants (N17Rac1, N17Cdc42).
- Administered C3 transferase, a Rho inhibitor.
Main Results:
- Constitutively active RhoA, Rac1, or Cdc42 inhibited cell migration due to impaired polarization.
- Inhibition of Rho (C3 transferase) or Rac (N17Rac1) significantly reduced CSF-1-induced migration speed.
- N17Cdc42-injected cells migrated but failed to polarize towards the CSF-1 gradient, abolishing chemotaxis.
Conclusions:
- Rho and Rac proteins are indispensable for the fundamental process of macrophage cell migration.
- Cdc42 is crucial for sensing and responding to chemoattractant gradients (CSF-1) but not for the act of locomotion itself.