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...
Main Authors: | , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2009-04-01
|
Series: | PLoS Pathogens |
Online Access: | http://europepmc.org/articles/PMC2660150?pdf=render |
id |
doaj-5d24deb3a1824ed184452a9f9e29264e |
---|---|
record_format |
Article |
spelling |
doaj-5d24deb3a1824ed184452a9f9e29264e2020-11-25T01:15:34ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742009-04-0154e100037010.1371/journal.ppat.1000370Morphogenesis of Strongyloides stercoralis infective larvae requires the DAF-16 ortholog FKTF-1.Michelle L CastellettoHolman C MasseyJames B LokBased 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.http://europepmc.org/articles/PMC2660150?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Michelle L Castelletto Holman C Massey James B Lok |
spellingShingle |
Michelle L Castelletto Holman C Massey James B Lok Morphogenesis of Strongyloides stercoralis infective larvae requires the DAF-16 ortholog FKTF-1. PLoS Pathogens |
author_facet |
Michelle L Castelletto Holman C Massey James B Lok |
author_sort |
Michelle L Castelletto |
title |
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_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_sort |
morphogenesis of strongyloides stercoralis infective larvae requires the daf-16 ortholog fktf-1. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2009-04-01 |
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. |
url |
http://europepmc.org/articles/PMC2660150?pdf=render |
work_keys_str_mv |
AT michellelcastelletto morphogenesisofstrongyloidesstercoralisinfectivelarvaerequiresthedaf16orthologfktf1 AT holmancmassey morphogenesisofstrongyloidesstercoralisinfectivelarvaerequiresthedaf16orthologfktf1 AT jamesblok morphogenesisofstrongyloidesstercoralisinfectivelarvaerequiresthedaf16orthologfktf1 |
_version_ |
1725152438109863936 |