title: Characterisation of major vault protein during the life cycle of the human parasite Schistosoma mansoni.
abstract: Vaults are ribonucleoproteins (13 MDa) highly conserved among lower and higher eukaryotes. Their association produces a complex composed of three proteins named Major Vault Protein (MVP), vault (PolyADP-ribose) polymerase (VPARP) and Telomerase-associated protein (TEP1), plus a small untranslated RNA. The exact function of this complex is unknown, although the biological role of vaults has been associated with multidrug resistance phenotypes and signal transduction pathways. Genomic analysis showed that model organisms, such as Caenorhabditis elegans and Drosophila melanogaster, do not possess genes encoding vaults. However, we have found that vault-related genes are present in the Schistosoma mansoni genome. These observations raised questions on the involvement of vaults in mechanisms of adaptation of the parasite in its mammalian host. Therefore, molecular characterisation of the putative Major Vault Protein performed using bioinformatics tools showed that this vault component is highly conserved in S. mansoni. The MVP expression level was quantified by qRT-PCR using total RNA from susceptible (LE) and resistant (LE-PZQ) adult worm lineages, cercariae and mechanically transformed schistosomula (MTS) cultured for 3.5, 24, 48 and 72 h in vitro. Our results suggest a stage-specific expression in all developmental stages analysed. Western blotting has shown up-regulation of SmMVP in the MTS-3.5, 72 h and resistant adult worms, and similar levels in all other stages. Furthermore, SmMVP was found differentially expressed in adult males and females from the susceptible lineage. Further studies should clarify whether SmMVP is somehow linked to drug resistance in S. mansoni.
authors.affiliation: Departamento de Ciências Biológicas, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Morro do Cruzeiro, Ouro Preto, MG, Brazil.
authors.forename: Eneida V
authors.initials: EV
authors.lastname: Reis
authors.forename: Roberta V
authors.initials: RV
authors.lastname: Pereira
authors.forename: Matheus
authors.initials: M
authors.lastname: Gomes
authors.forename: Liana K
authors.initials: LK
authors.lastname: Jannotti-Passos
authors.forename: Elio H
authors.initials: EH
authors.lastname: Baba
authors.forename: Paulo Marcos Zech
authors.initials: PM
authors.lastname: Coelho
authors.forename: Ana C A
authors.initials: AC
authors.lastname: Mattos
authors.forename: Flávia F B
authors.initials: FF
authors.lastname: Couto
authors.forename: William
authors.initials: W
authors.lastname: Castro-Borges
authors.forename: Renata
authors.initials: R
authors.lastname: Guerra-Sá
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology; D016208:Databases, Factual; D004351:Drug Resistance; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D008018:Life Cycle Stages / Q000502:physiology*; D008297:Male; D011223:Praziquantel / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012550:Schistosoma mansoni / Q000187:drug effects / Q000502:physiology*; D020394:Vault Ribonucleoprotein Particles / Q000235:genetics / Q000378:metabolism*; D000099187:Major Vault Protein
chemical_list: D000871:Anthelmintics; D011223:Praziquantel; D012333:RNA, Messenger; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein
keywords: Differential expression; MVP protein; Resistance; Schistosoma mansoni; Vault complex