RRC ID 45965
Author Fancsalszky L, Monostori E, Farkas Z, Pourkarimi E, Masoudi N, Hargitai B, Bosnar MH, Deželjin M, Zsákai A, Vellai T, Mehta A, Takács-Vellai K.
Title NDK-1, the homolog of NM23-H1/H2 regulates cell migration and apoptotic engulfment in C. elegans.
Journal PLoS One
Abstract Abnormal regulation of cell migration and altered rearrangement of cytoskeleton are characteristic of metastatic cells. The first described suppressor of metastatic processes is NM23-H1, which displays NDPK (nucleoside-diphosphate kinase) activity. To better understand the role of nm23 genes in cell migration, we investigated the function of NDK-1, the sole Caenorhabditis elegans homolog of group I NDPKs in distal tip cell (DTC) migration. Dorsal phase of DTC migration is regulated by integrin mediated signaling. We find that ndk-1 loss of function mutants show defects in this phase. Epistasis analysis using mutants of the α-integrin ina-1 and the downstream functioning motility-promoting signaling module (referred to as CED-10 pathway) placed NDK-1 downstream of CED-10/Rac. As DTC migration and engulfment of apoptotic corpses are analogous processes, both partially regulated by the CED-10 pathway, we investigated defects of apoptosis in ndk-1 mutants. Embryos and germ cells defective for NDK-1 showed an accumulation of apoptotic cell corpses. Furthermore, NDK-1::GFP is expressed in gonadal sheath cells, specialized cells for engulfment and clearence of apoptotic corpses in germ line, which indicates a role for NDK-1 in apoptotic corpse removal. In addition to the CED-10 pathway, engulfment in the worm is also mediated by the CED-1 pathway. abl-1/Abl and abi-1/Abi, which function in parallel to both CED-10/CED-1 pathways, also regulate engulfment and DTC migration. ndk-1(-);abi-1(-) double mutant embryos display an additive phenotype (e. g. enhanced number of apoptotic corpses) which suggests that ndk-1 acts in parallel to abi-1. Corpse number in ndk-1(-);ced-10(-) double mutants, however, is similar to ced-10(-) single mutants, suggesting that ndk-1 acts downstream of ced-10 during engulfment. In addition, NDK-1 shows a genetic interaction with DYN-1/dynamin, a downstream component of the CED-1 pathway. In summary, we propose that NDK-1/NDPK might represent a converging point of CED-10 and CED-1 pathways in the process of cytoskeleton rearrangement.
Volume 9(3)
Pages e92687
Published 2014-1-1
DOI 10.1371/journal.pone.0092687
PII PONE-D-13-48162
PMID 24658123
PMC PMC3962447
MeSH Animals Animals, Genetically Modified Apoptosis / genetics* Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Cell Line Cell Movement / genetics* Cytoskeletal Proteins / genetics Cytoskeletal Proteins / metabolism Embryo, Nonmammalian / metabolism Genes, Lethal Humans Mutation NM23 Nucleoside Diphosphate Kinases / genetics* NM23 Nucleoside Diphosphate Kinases / metabolism* Phenotype Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Signal Transduction rac GTP-Binding Proteins / genetics rac GTP-Binding Proteins / metabolism
IF 2.74
Times Cited 16
WOS Category CELL BIOLOGY
Resource
C.elegans tm494