A CDC-42-regulated actin network is necessary for nuclear migration through constricted spaces inC. elegans

Abstract

AbstractSuccessful nuclear migration through constricted spaces between cells or in the extracellular matrix relies on the ability of the nucleus to deform. Little is known of how this takes placein vivo. We study confined nuclear migration inCaenorhabditis eleganslarval P-cells, which is mediated by the LINC complex to pull nuclei towards the minus ends of microtubules. Null mutations of LINC componentunc-84lead to a temperature-dependent phenotype, suggesting a parallel pathway for P-cell nuclear migration. A forward genetic screen for enhancers ofunc-84identifiedcgef-1(CDC-42Guanine NucleotideExchangeFactor). 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 rescued nuclear migration incgef-1; unc-84double mutants suggesting 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, induces actin polymerization through the Arp2/3 complex to deform the nucleus during nuclear migration while NMY-2 helps push the nucleus through confined spaces.