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PLoS Negl Trop Dis. 2014 Jun 19;8(6):e2949. doi: 10.1371/journal.pntd.0002949. eCollection 2014 Jun.

Regulation of Schistosoma mansoni development and reproduction by the mitogen-activated protein kinase signaling pathway.

Author information

1
Grupo de Genômica e Biologia Computacional, Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais and Centro de Excelência em Bioinformática- CEBio, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz - FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
2
Biologia Parasitária, Departamento de Ensino, Pavilhão Arthur Neiva, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil; Laboratório de Helmintologia Romero Lascasas Porto, Departamento de Patologia e Laboratórios, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
3
Laboratório de Helmintologia Romero Lascasas Porto, Departamento de Patologia e Laboratórios, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
4
Laboratório de Esquistossomose Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz - FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
5
Laboratório de Entomologia Médica, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz - FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
6
Center for Discovery and Innovation in Parasitic Diseases, California Institute for Quantitative Biosciences and the Department of Pathology, University of California, San Francisco, San Francisco, California, United States of America.

Erratum in

  • PLoS Negl Trop Dis. 2014 Jul;8(7):e3081.

Abstract

BACKGROUND:

Protein kinases are proven targets for drug development with an increasing number of eukaryotic Protein Kinase (ePK) inhibitors now approved as drugs. Mitogen-activated protein kinase (MAPK) family members connect cell-surface receptors to regulatory targets within cells and influence a number of tissue-specific biological activities such as cell proliferation, differentiation and survival. However, the contributions of members of the MAPK pathway to schistosome development and survival are unclear.

METHODOLOGY/PRINCIPAL FINDINGS:

We employed RNA interference (RNAi) to elucidate the functional roles of five S. mansoni genes (SmCaMK2, SmJNK, SmERK1, SmERK2 and SmRas) involved in MAPK signaling pathway. Mice were injected with post-infective larvae (schistosomula) subsequent to RNAi and the development of adult worms observed. The data demonstrate that SmJNK participates in parasite maturation and survival of the parasites, whereas SmERK are involved in egg production as infected mice had significantly lower egg burdens with female worms presenting underdeveloped ovaries. Furthermore, it was shown that the c-fos transcription factor was overexpressed in parasites submitted to RNAi of SmERK1, SmJNK and SmCaMK2 indicating its putative involvement in gene regulation in this parasite's MAPK signaling cascade.

CONCLUSIONS:

We conclude that MAPKs proteins play important roles in the parasite in vivo survival, being essential for normal development and successful survival and reproduction of the schistosome parasite. Moreover SmERK and SmJNK are potential targets for drug development.

PMID:
24945272
PMCID:
PMC4063740
DOI:
10.1371/journal.pntd.0002949
[Indexed for MEDLINE]
Free PMC Article

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