Exploring the role of two interacting phosphoinositide 3-kinases of Haemonchus contortus

Li, Fa-Cai; Gasser, Robin B.; Lok, James B.; Korhonen, Pasi K.; Wang, Yifan; Yin, Fangyuan; Li, He; Zhou, Rui; Zhao, Jiewen; Hu, Min

doi:10.1186/preaccept-5374662301417597

Cited by 5 publications

(11 citation statements)

References 57 publications

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“…28 Hc-akt-1b transcription was highest in L3s, suggesting that it might relate to developmental arrest in this stage. These results are consistent with those of other genes, such as Hc-age-1, Hc-aap-1, Hc-daf-2, and Hc-pdk-1 in the insulin-like signaling pathway of H. contortus, 11,31,32 and Ss-akt-1, Ss-age-1, Ss-daf-2b, and Ss-pdk-1 in S. stercoralis. 10,33,34 Both Ce-akt-1 and Ce-akt-2…”

Section: Discussionsupporting

confidence: 89%

A serine/threonine‐specific protein kinase ofHaemonchus contortuswith a role in the development

Gasser

et al. 2019

FASEB j.

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In the free‐living nematode Caenorhabditis elegans, the serine/threonine‐specific protein kinase, AKT, is known to play a key role in dauer formation, life‐span, and stress‐resistance through the insulin‐like signaling pathway. Although the structure and function of AKT‐coding genes of C. elegans are understood, this is not the case for homologous genes in parasitic nematodes. In the present study, we explored a C. elegans akt‐1 gene homolog in the parasitic nematode Haemonchus contortus, investigated its transcript isoforms (Hc‐akt‐1a and Hc‐akt‐1b), and studied expression and function using both homologous and heterologous functional genomic tools. In C. elegans, we showed that the predicted promoter of Hc‐akt‐1 drives substantial expression in ASJ neurons of the N2 (wild‐type) strain. In H. contortus (Haecon‐5 stain), RNAi (soaking) led to a significantly decreased transcript abundance for both Hc‐akt‐1a and Hc‐akt‐1b, and reduced larval development in larval stages in vitro. Chemical inhibition was also shown to block larval development. Taken together, the evidence from this study points to a key functional role for Hc‐akt‐1 in H. contortus.

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Section: Discussionsupporting

confidence: 89%

A serine/threonine‐specific protein kinase ofHaemonchus contortuswith a role in the development

Gasser

et al. 2019

FASEB j.

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“…The genomes and transcriptomes of H. contortus [ 23 , 24 ] provide a solid foundation for exploring key molecules in this transition process, but a lack of effective genetic and in vitro culture methods restricts somewhat the study of molecular mechanisms of these nematodes [ 25 – 27 ]. In contrast, C. elegans has been used as a surrogate system to explore molecular functions in some parasitic nematodes, such as H. contortus [ 28 – 30 ], Ancylostoma caninum [ 31 , 32 ] and Strongyloides stercoralis [ 33 , 34 ]. In the present study, we isolated and characterized the pdk-1 ortholog from H. contortus ( Hc-pdk-1 ).…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization of the Haemonchus contortus phosphoinositide-dependent protein kinase-1 gene (Hc-pdk-1)

Gasser

Lok

et al. 2016

Parasites Vectors

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BackgroundPhosphoinositide-dependent protein kinase-1 (PDK-1), which functions downstream of phosphoinositide 3-kinase (AGE-1) and activates protein kinases of the AGC family, plays critical roles in regulating biology processes, such as metabolism, growth, development and survival. In the free-living nematode Caenorhabditis elegans, PDK-1 is a key component of the insulin-like signalling pathway, regulating the entry into and exit from dauer (arrested development). Although it is proposed that similar molecular mechanisms control the transition from the free-living to the parasitic stages of nematodes, nothing is known about PDK-1 in Haemonchus contortus, a socioeconomically important gastric nematode of ruminants.MethodsHere, we isolated and characterized the pdk-1 gene (Hc-pdk-1) and its inferred product (Hc-PDK-1) from H. contortus. Using in vitro and in vivo methods, we then studied the transcriptional profiles of Hc-pdk-1 and anatomical gene expression patterns of Hc-PDK-1 in different developmental stages of C. elegans.ResultsIn silico analysis of Hc-PDK-1 displayed conserved functional domains, such as protein kinase and pleckstrin homology (PH) domains and two predicted phosphorylation sites (Thr226/Tyr229), which are crucial for the phosphorylation of downstream signalling. The Hc-pdk-1 gene is transcribed in all of the main developmental stages of H. contortus, with its highest transcription in the infective third-stage larvae (iL3) compared with other stages. Transgene constructs, in which respective promoters were fused to the coding sequence for green fluorescent protein (GFP), were used to transform C. elegans, and to localize and compare the expression of Hc-pdk-1 and Ce-pdk-1. The expression of GFP under the control of the Hc-pdk-1 promoter was localized to the intestine, and head and tail neurons, contrasting somewhat the profile for the C. elegans ortholog, which is expressed in pharynx, intestine and head and tail neurons.ConclusionsThis is the first characterization of pdk-1/PDK-1 from a trichostrongyloid nematode. Taken together, the findings from this study provide a first glimpse of the involvement of Hc-pdk-1 in the insulin-like signalling pathway in H. contortus.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1351-6) contains supplementary material, which is available to authorized users.

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“…While much is known about the IIS pathway in C. elegans (reviewed in [ 31 ]), only a few studies have explored the functions of selected parts of this pathway in H. contortus [ 32 – 34 ], and no study has yet investigated its full composition in this parasitic nematode. Therefore, in the present study, we (i) curated the full-length open reading frames (ORFs) and defined the complement of genes that encode peptides/proteins involved in IIS, (ii) studied the interactions of these genes and (iii) examined their transcription profiles in all key developmental stages of H. contortus .…”

Section: Introductionmentioning

confidence: 99%

Reconstruction of the insulin-like signalling pathway of Haemonchus contortus

Mohandas

Stroehlein

et al. 2016

Parasites Vectors

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BackgroundIn the present study, we reconstructed the insulin/insulin-like growth factor 1 signalling (IIS) pathway for Haemonchus contortus, which is one of the most important eukaryotic pathogens of livestock worldwide and is related to the free-living nematode Caenorhabditis elegans.MethodsWe curated full-length open-reading frames from assembled transcripts, defined the complement of genes that encode proteins involved in this pathway and then investigated the transcription profiles of these genes for all key developmental stages of H. contortus.ResultsThe core components of the IIS pathway are similar to their respective homologs in C. elegans. However, there is considerable variation in the numbers of isoforms between H. contortus and C. elegans and an absence of AKT-2 and DDL-2 homologs from H. contortus. Interestingly, DAF-16 has a single isoform in H. contortus compared with 12 in C. elegans, suggesting novel functional roles in the parasitic nematode. Some IIS proteins, such as DAF-18 and SGK-1, vary in their functional domains, indicating distinct roles from their homologs in C. elegans.ConclusionsThis study paves the way for the further characterization of key signalling pathways in other socioeconomically important parasites and should help understand the complex mechanisms involved in developmental processes.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1341-8) contains supplementary material, which is available to authorized users.

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Exploring the role of two interacting phosphoinositide 3-kinases of Haemonchus contortus

Cited by 5 publications

References 57 publications

A serine/threonine‐specific protein kinase ofHaemonchus contortuswith a role in the development

A serine/threonine‐specific protein kinase ofHaemonchus contortuswith a role in the development

Molecular characterization of the Haemonchus contortus phosphoinositide-dependent protein kinase-1 gene (Hc-pdk-1)

Reconstruction of the insulin-like signalling pathway of Haemonchus contortus

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