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

Redox-sensitive CDC-42 clustering promotes wound closure in C. elegans.
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DOI:
10.1016/j.celrep.2021.110040
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发表时间:
2021-11-23
期刊:
影响因子:
8.8
通讯作者:
Xu S
Xu S
中科院分区:
生物学1区
文献类型:
--
作者:
Xu J;Meng X;Yang Q;Zhang J;Hu W;Fu H;Chen JW;Ma W;Chisholm AD;Sun Q;Xu S

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Tissue damage induces immediate-early signals, activating Rho small GTPases to trigger actin polymerization essential for later wound repair. However, how tissue damage is sensed to activate Rho small GTPases locally remains elusive. Here, we found that wounding the C. elegans epidermis induces rapid relocalization of CDC-42 into plasma membrane-associated clusters, which subsequently recruits WASP/WSP-1 to trigger actin polymerization to close the wound. In addition, wounding induces a local transient increase and subsequent reduction of H2O2, which negatively regulates the clustering of CDC-42 and wound closure. CDC-42 CAAX motif-mediated prenylation and polybasic region-mediated cation-phospholipid interaction are both required for its clustering. Cysteine residues participate in intermolecular disulfide bonds to reduce membrane association and are required for negative regulation of CDC-42 clustering by H2O2. Collectively, our findings suggest that H2O2-regulated fine-tuning of CDC-42 localization can create a distinct biomolecular cluster that facilitates rapid epithelial wound repair after injury. Tissues must immediately detect and respond to injury before repairing the damage. Here, Xu et al. report that wounding induced a local increase and subsequent reduction of H2O2. This regulates fine-tuning of CDC-42 clustering to recruit WSP-1 and promote actin polymerization-based wound closure in C. elegans epidermis.
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