title: Identification and characterization of functional Smad8 and Smad4 homologues from Echinococcus granulosus.
abstract: Smad family proteins are essential cellular mediators of the transforming growth factor-β superfamily. In the present study, we identified two members of the Smad proteins, Smad8 and Smad4 homologues (termed as EgSmadE and EgSmadD, respectively), from Echinococcus granulosus, the causative agent of cystic echinococcosis (CE). Phylogenetic analysis placed EgSmadE in the Smad1, 5, and 8 subgroup of the R-Smad sub-family and EgSmadD in the Co-Smad family. Furthermore, EgSmadE and EgSmadD attained a high homology to EmSmadE and EmSmadD of E. multilocularis, respectively. Both EgSmadE and EgSmadD were co-expressed in the larval stages and exhibited the highest transcript levels in activated protoscoleces, and their encoded proteins were co-localized in the sub-tegumental and tegumental layer of the parasite. As shown by yeast two-hybrid and pull-down analysis, EgSmadE displayed a positive binding interaction with EgSmadD. In addition, EgSmadE localized in the nuclei of Mv1Lu cells (mink lung epithelial cells) upon treatment with human TGF-β1 or human BMP2, indicating that EgSmadE is capable of being translocated into nucleus, in vitro. Our study suggests that EgSmadE and EgSmadD may take part in critical biological processes, including echinococcal growth, development, and parasite-host interaction.
authors.affiliation: Xinjiang Key Laboratory of Echinococcosis, The First Affiliated Hospital of Xinjiang Medical University, No.137 Liyushan South Road, Urumqi, 830054, Xinjiang, China.
authors.forename: Chuanshan
authors.initials: C
authors.lastname: Zhang
authors.forename: Limin
authors.initials: L
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Hongwei
authors.initials: H
authors.lastname: Pu
authors.forename: Le
authors.initials: L
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Junhua
authors.initials: J
authors.lastname: Wang
authors.forename: Guodong
authors.initials: G
authors.lastname: Lü
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Lu
authors.forename: Wenbao
authors.initials: W
authors.lastname: Zhang
authors.forename: Dominique A
authors.initials: DA
authors.lastname: Vuitton
authors.forename: Hao
authors.initials: H
authors.lastname: Wen
authors.forename: Renyong
authors.initials: R
authors.lastname: Lin
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D018509:DNA, Helminth / Q000737:chemistry / Q000235:genetics; D004443:Echinococcosis / Q000469:parasitology*; D048209:Echinococcus granulosus / Q000145:classification / Q000235:genetics* / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D049751:Genome, Helminth / Q000235:genetics; D015801:Helminth Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006790:Host-Parasite Interactions; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D010802:Phylogeny; D011817:Rabbits; D015398:Signal Transduction; D051901:Smad4 Protein / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D051904:Smad8 Protein / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D018509:DNA, Helminth; D015801:Helminth Proteins; D007106:Immune Sera; D051901:Smad4 Protein; D051904:Smad8 Protein; D053773:Transforming Growth Factor beta1