Redox-sensitive CDC-42 clustering promotes wound closure in C. elegans

Area of Science:

• Cell Biology
• Molecular Biology
• Developmental Biology

Background:

• Tissue damage triggers immediate-early signals involving Rho small GTPases for wound repair.
• The precise mechanism of sensing tissue damage to locally activate Rho GTPases is not fully understood.

Purpose of the Study:

• To investigate how tissue damage is sensed to activate Rho GTPases, specifically CDC-42, in C. elegans epidermis.
• To elucidate the role of hydrogen peroxide (H2O2) in regulating CDC-42 localization and wound closure.

Main Methods:

• Wounding the C. elegans epidermis to observe cellular responses.
• Analyzing the relocalization of CDC-42 and its interaction with WASP/WSP-1.
• Measuring local H2O2 levels and their impact on CDC-42 clustering and wound repair.
• Investigating the roles of CDC-42 prenylation, polybasic region, and cysteine residues in its membrane association and regulation.

Main Results:

• Wounding induces rapid CDC-42 relocalization into plasma membrane clusters, recruiting WASP/WSP-1 to promote actin polymerization and wound closure.
• A transient increase and subsequent decrease in local H2O2 levels negatively regulate CDC-42 clustering and impair wound closure.
• CDC-42 clustering requires CAAX motif prenylation and polybasic region-mediated interactions.
• Cysteine residues form disulfide bonds, reducing membrane association and mediating H2O2's negative regulation of CDC-42 clustering.

Conclusions:

• H2O2-regulated fine-tuning of CDC-42 localization is crucial for forming biomolecular clusters that facilitate rapid epithelial wound repair.
• The study reveals a novel mechanism linking oxidative stress signaling to Rho GTPase activity for tissue repair.