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Morphogenesis of Strongyloides stercoralis Infective Larvae Requires the DAF-16 Ortholog FKTF-1
Based on metabolic and morphological similarities between infective third-stage larvae of parasitic nematodes and dauer larvae of Caenorhabditis elegans, it is hypothesized that similar genetic mechanisms control the development of these forms. In the parasite Strongyloides stercoralis, FKTF-1 is an...
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2660150/ https://www.ncbi.nlm.nih.gov/pubmed/19360119 http://dx.doi.org/10.1371/journal.ppat.1000370 |
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author | Castelletto, Michelle L. Massey, Holman C. Lok, James B. |
author_facet | Castelletto, Michelle L. Massey, Holman C. Lok, James B. |
author_sort | Castelletto, Michelle L. |
collection | PubMed |
description | Based on metabolic and morphological similarities between infective third-stage larvae of parasitic nematodes and dauer larvae of Caenorhabditis elegans, it is hypothesized that similar genetic mechanisms control the development of these forms. In the parasite Strongyloides stercoralis, FKTF-1 is an ortholog of DAF-16, a forkhead transcription factor that regulates dauer larval development in C. elegans. Using transgenesis, we investigated the role of FKTF-1 in S. stercoralis' infective larval development. In first-stage larvae, GFP-tagged recombinant FKTF-1b localizes to the pharynx and hypodermis, tissues remodeled in infective larvae. Activating and inactivating mutations at predicted AKT phosphorylation sites on FKTF-1b give constitutive cytoplasmic and nuclear localization of the protein, respectively, indicating that its post-translational regulation is similar to other FOXO-class transcription factors. Mutant constructs designed to interfere with endogenous FKTF-1b function altered the intestinal and pharyngeal development of the larvae and resulted in some transgenic larvae failing to arrest in the infective stage. Our findings indicate that FKTF-1b is required for proper morphogenesis of S. stercoralis infective larvae and support the overall hypothesis of similar regulation of dauer development in C. elegans and the formation of infective larvae in parasitic nematodes. |
format | Text |
id | pubmed-2660150 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-26601502009-04-10 Morphogenesis of Strongyloides stercoralis Infective Larvae Requires the DAF-16 Ortholog FKTF-1 Castelletto, Michelle L. Massey, Holman C. Lok, James B. PLoS Pathog Research Article Based on metabolic and morphological similarities between infective third-stage larvae of parasitic nematodes and dauer larvae of Caenorhabditis elegans, it is hypothesized that similar genetic mechanisms control the development of these forms. In the parasite Strongyloides stercoralis, FKTF-1 is an ortholog of DAF-16, a forkhead transcription factor that regulates dauer larval development in C. elegans. Using transgenesis, we investigated the role of FKTF-1 in S. stercoralis' infective larval development. In first-stage larvae, GFP-tagged recombinant FKTF-1b localizes to the pharynx and hypodermis, tissues remodeled in infective larvae. Activating and inactivating mutations at predicted AKT phosphorylation sites on FKTF-1b give constitutive cytoplasmic and nuclear localization of the protein, respectively, indicating that its post-translational regulation is similar to other FOXO-class transcription factors. Mutant constructs designed to interfere with endogenous FKTF-1b function altered the intestinal and pharyngeal development of the larvae and resulted in some transgenic larvae failing to arrest in the infective stage. Our findings indicate that FKTF-1b is required for proper morphogenesis of S. stercoralis infective larvae and support the overall hypothesis of similar regulation of dauer development in C. elegans and the formation of infective larvae in parasitic nematodes. Public Library of Science 2009-04-10 /pmc/articles/PMC2660150/ /pubmed/19360119 http://dx.doi.org/10.1371/journal.ppat.1000370 Text en Castelletto et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Castelletto, Michelle L. Massey, Holman C. Lok, James B. Morphogenesis of Strongyloides stercoralis Infective Larvae Requires the DAF-16 Ortholog FKTF-1 |
title | Morphogenesis of Strongyloides stercoralis Infective Larvae Requires the DAF-16 Ortholog FKTF-1 |
title_full | Morphogenesis of Strongyloides stercoralis Infective Larvae Requires the DAF-16 Ortholog FKTF-1 |
title_fullStr | Morphogenesis of Strongyloides stercoralis Infective Larvae Requires the DAF-16 Ortholog FKTF-1 |
title_full_unstemmed | Morphogenesis of Strongyloides stercoralis Infective Larvae Requires the DAF-16 Ortholog FKTF-1 |
title_short | Morphogenesis of Strongyloides stercoralis Infective Larvae Requires the DAF-16 Ortholog FKTF-1 |
title_sort | morphogenesis of strongyloides stercoralis infective larvae requires the daf-16 ortholog fktf-1 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2660150/ https://www.ncbi.nlm.nih.gov/pubmed/19360119 http://dx.doi.org/10.1371/journal.ppat.1000370 |
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