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Actin and CDC-42 contribute to nuclear migration through constricted spaces in C. elegans.

Jamie Ho | Leslie A Guerrero | Diana E Libuda | G W Gant Luxton | Daniel A Starr
Development (Cambridge, England) | 2023

Successful nuclear migration through constricted spaces between cells or in the extracellular matrix relies on the ability of the nucleus to deform. Little is known about how this takes place in vivo. We have studied confined nuclear migration in Caenorhabditis elegans larval P cells, which is mediated by the LINC complex to pull nuclei towards the minus ends of microtubules. Null mutations of the LINC component unc-84 lead to a temperature-dependent phenotype, suggesting a parallel pathway for P-cell nuclear migration. A forward genetic screen for enhancers of unc-84 identified cgef-1 (CDC-42 guanine nucleotide exchange factor). Knockdown of CDC-42 in the absence of the LINC complex led to a P-cell nuclear migration defect. Expression of constitutively active CDC-42 partially rescued nuclear migration in cgef-1; unc-84 double mutants, suggesting that CDC-42 functions downstream of CGEF-1. The Arp2/3 complex and non-muscle myosin II (NMY-2) were also found to function parallel to the LINC pathway. In our model, CGEF-1 activates CDC-42, which induces actin polymerization through the Arp2/3 complex to deform the nucleus during nuclear migration, and NMY-2 helps to push the nucleus through confined spaces.

Pubmed ID: 37756590

Associated grants

  • Agency: NIH HHS, United States
    Id: S10 OD026702
  • Agency: NIGMS NIH HHS, United States
    Id: R35 GM128890
  • Agency: NIH HHS, United States
    Id: P40 OD010440
  • Agency: NIGMS NIH HHS, United States
    Id: R35 GM134859

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