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NDK-1, the Homolog of NM23-H1/H2 Regulates Cell Migration and Apoptotic Engulfment in C. elegans

Fanczalszky, Luca; Monostori, Eszter; Farkas, Zsolt; Masoudi, Neda; Hargitai, Balazs; Herak Bosnar, Maja; Deželjin, Martina; Zsakai, Annamaria; Vella, Tibor; Mehta, Anil; Mehta, Anil; Takacz-Vellai, Krisztina (2014) NDK-1, the Homolog of NM23-H1/H2 Regulates Cell Migration and Apoptotic Engulfment in C. elegans. PLoS ONE, 9 (3). e92687/1-e92687/12. ISSN 1932-6203

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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.

Item Type: Article
Uncontrolled Keywords: NDK; nm23; C. elegans; apoptotic engulfment
Subjects: BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
Divisions: Division of Molecular Medicine
Projects:
Project titleProject leaderProject codeProject type
Uloga gena nm23 u karcinomu pločastog epitela usne šupljine[202030] Maja Herak-Bosnar098-0982464-2513MZOS
Depositing User: Maja Herak Bosnar
Date Deposited: 09 Jul 2015 08:53
Last Modified: 09 Jul 2015 08:53
URI: http://fulir.irb.hr/id/eprint/2042
DOI: 10.1371/journal.pone.0092687

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