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Updated: Jul 25, 2026
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Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
Published on: March 9, 2012
Rac1 mediates collapsin-1-induced growth cone collapse
1Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Summary
Collapsin-1 inhibits axonal outgrowth by collapsing neuronal growth cones. Rho and Rac1 GTPases are key mediators, with Rac1 potentially playing a central role in Collapsin-1 signaling pathways.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Collapsin-1 (semaphorin III(D)) inhibits axonal outgrowth by inducing growth cone collapse.
- Growth cone collapse is linked to actin depolymerization, suggesting a role for small GTP-binding proteins.
Purpose of the Study:
- To investigate the role of rho subfamily GTP-binding proteins in collapsin-1 signal transduction.
- To determine the specific involvement of Rho, Rac1, and Cdc42 in growth cone motility and response to collapsin-1.
Main Methods:
- Introduction of recombinant Rho, Rac1, and Cdc42 proteins into embryonic chick dorsal root ganglion (DRG) neurons.
- Utilizing constitutively active and dominant-negative forms of Rac1 and Cdc42.
- Employing Clostridium botulinum C3 transferase to inhibit Rho activity.
Main Results:
- Dominant-negative Rac1 inhibited collapsin-1-induced growth cone collapse and neurite outgrowth inhibition.
- Rac1 activation increased growth cone collapse, while Cdc42 had no significant effect.
- Rho inhibition via C3 transferase stimulated neurite outgrowth but impaired growth cone spreading and responsiveness to collapsin-1 and myelin.
Conclusions:
- Rho and Rac1 GTPases play significant roles in regulating neuronal growth cone motility.
- Rac1 appears to be a key mediator of collapsin-1's inhibitory effects on axonal outgrowth.
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