A serine/threonine‐specific protein kinase of<i>Haemonchus contortus</i>with a role in the development

Di, Wenda; Gasser, Robin B.; He, Li; Li, Fangfang; Liu, Xiaofang; Zhou, Caixian; Zhou, Yanqin; Fang, Rui; Zhao, Junlong; Hu, Min

doi:10.1096/fj.201900888rr

Cited by 13 publications

(11 citation statements)

References 39 publications

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“…The experimental group treated with specific siRNAs showed fewer developed worms because the buccal development failed to initiate. This is the same effect as described for the knockdown of Hc-daf-3 and Hc-akt-1 [ 38 , 39 ], and suggests that Hc-daf-5 functions in the development from xL3 to L4.…”

Section: Discussionsupporting

confidence: 77%

A transcription factor DAF-5 functions in Haemonchus contortus development

et al. 2021

Parasites Vectors

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Background Abnormal dauer formation gene (daf-5), located downstream of the DAF-7 signalling pathway, mainly functions in dauer formation and reproductive processes in the free-living nematode Caenorhabditis elegans. Although the structure and function of daf-5 have been clarified in C. elegans, they still remain totally unknown in Haemonchus contortus, a socio-economically important parasitic nematode of gastric ruminants. Methods A homologue of daf-5, Hc-daf-5, and its inferred product (Hc-DAF-5) in H. contortus were identified and characterized in this study. Then the transcriptional profiles of Hc-daf-5 and the anatomical expression of Hc-DAF-5 in H. contortus were studied using an integrated molecular approach. RNA interference (RNAi) was performed to explore its function in transition from the exsheathed third-stage larvae (xL3s) to the fourth-stage larvae (L4s) in vitro. Finally, the interaction between Hc-DAF-5 and Hc-DAF-3 (a co-Smad) was detected by bimolecular fluorescence complementation (BiFc) in vitro. Results It was shown that Hc-DAF-5 was a member of the Sno/Ski superfamily. Hc-daf-5 was transcribed in all developmental stages of H. contortus, with significant upregulation in L3s. Native Hc-DAF-5 was localized in the reproductive organs, cuticle, and intestine via immunohistochemistry. RNAi revealed that specific small interfering RNAs (siRNAs) could retard xL3 development. In addition, the interaction between Hc-DAF-5 and Hc-DAF-3 indicated that the SDS box of Hc-DAF-5 was dispensable for the binding of Hc-DAF-5 to Hc-DAF-3, and the MH2 domain was the binding region between Hc-DAF-3 and Hc-DAF-5. Conclusions In summary, these findings show that Hc-daf-5 functions in the developmental processes of H. contortus, and this study is the first attempt to characterize the daf-5 gene in parasitic nematodes. Graphical abstract

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Section: Discussionsupporting

confidence: 77%

A transcription factor DAF-5 functions in Haemonchus contortus development

et al. 2021

Parasites Vectors

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“…3E). These results suggest a role of HcSMA2 in differentiation of infective xL3 to L4 larvae, which is consistent with the function of the known members of the TGF-β and Insulin signaling [8][9][10][11][12]23]. In C. elegans, CeSMA2 regulates the body size [24], morphogenesis of the male worm's tail tip [25], as well as reproductive aging [21,26].…”

Section: Hcsma2 Transcript Is Upregulated In the Adult Male Wormssupporting

confidence: 70%

A novel BR-SMAD is required for larval development in barber’s pole worm Haemonchus contortus

Li¹,

Qin²,

Ye³

et al. 2021

Microb Cell

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SMAD proteins mediate TGF-β signaling and thereby regulate the metazoan development; however, they are poorly defined in Haemonchus contortus–a common blood-sucking parasitic nematode of small ruminants. Here, we characterized an R-SMAD family protein in H. contortus termed HcSMA2, which is closely related to Caenorhabditis elegans SMA2 (CeSMA2) involved in the bone morphogenetic protein (BMP) signaling. Hcsma2 is transcribed in all developmental stages of H. contortus but highly induced in the adult male worms. The RNA interference with Hcsma2 retarded the transition of infective L3 into L4 larvae. Besides, the bimolecular fluorescence complementation revealed the interaction of HcSMA2 with a TGF-β-activated-R-SMAD (HcDAF8). Together these results show a BMP-like receptor-regulated SMAD in H. contortus that is required for larval differentiation and underscore an adaptive functional repurposing of BMP-signaling in parasitic worms.

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“…Considering the high transcription level of Hcdaf5 in L3, RNAi mediate by siRNA was performed to explore its role in transition from the free-living stage (xL3) to the parasitic stage (L4). Here, silencing of Hcdaf5 decreased the developmental rate of xL3, as speci c siRNA-treated group showed less worms developed, for which buccal development failed to initiate, same as the Hcdaf3 and Hcakt1 [23,24], suggesting that Hcdaf5 functions in the development of xL3 to L4.…”

Section: Discussionmentioning

confidence: 67%

“…The H. contortus Hacon-5 strain was maintained by goats, which were infected orally with 5,000 L3 (Di et al, 2020). Free-living stages including eggs, rst-stage larvae (L1), second-stage larvae (L2) and L3s were harvested from faeces of infected goats.…”

Section: Worm Maintenancementioning

confidence: 99%

A Transcription Factor DAF5 Functions in Haemonchus Contortus Development

et al. 2021

Preprint

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Background: Daf5 (Dauer abnormal formation gene), located in the downstream of DAF-7 signalling pathway, mainly functions in dauer formation and reproductive processes in the free-living nematode Caenorhabditis elegans. Although its structure and function have been studied clearly in C. elegans, it was totally unknown in Haemonchus contortus, a socio-economically important parasitic nematode of gastric ruminants.Methods: Here, we identified and characterized a homologue of Daf5, Hcdaf5 and its inferred product (HcDAF5) in H. contortus. Using an integrated molecular approach, we studied the transcriptional profiles of Hcdaf5 and the anatomical expression of HcDAF5 in H. contortus. RNA interference (RNAi) was performed to explore its function in transition from the exsheathed third-stage larvae (xL3) to the fourth-stage larvae (L4) in vitro. Interaction of HcDAF5 and HcDAF3 (a co-SMAD) was also detected by bimolecular fluorescence complementation system (BiFc) in vitro.Results: Here, we showed that HcDAF5 is a member of the Sno/Ski superfamily. Hcdaf5 was transcribed in all developmental stages of H. contortus, with a significant up-regulation in L3. Immunohistochemistry localized native HcDAF5 to the reproductive organs, cuticle and intestine. RNAi revealed specific siRNAs (small interfering RNA) could retard the xL3 development. In addition, the interaction between HcDAF5 and HcDAF3 indicated the SDS box region of HcDAF5 is dispensable for the binding of HcDAF5 to HcDAF3 and the region in HcDAF3 that binds to HcDAF5 is MH2 domain.Conclusion: In summary, these findings show that Hcdaf5 functions in developmental processes of H. contortus, and this is the first characterization of daf-5 gene in parasitic nematodes.

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

Cited by 13 publications

References 39 publications

A transcription factor DAF-5 functions in Haemonchus contortus development

A transcription factor DAF-5 functions in Haemonchus contortus development

A novel BR-SMAD is required for larval development in barber’s pole worm Haemonchus contortus

A Transcription Factor DAF5 Functions in Haemonchus Contortus Development

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