title: The first characterization of multidrug and toxin extrusion (MATE/SLC47) proteins in zebrafish (Danio rerio).
abstract: Multidrug and toxin extrusion (MATE) proteins are involved in the extrusion of endogenous compounds and xenobiotics across the plasma membrane. They are conserved from bacteria to mammals, with different numbers of genes within groups. Here, we present the first data on identification and functional characterization of Mate proteins in zebrafish (Danio rerio). Phylogenetic analysis revealed six Mates in teleost fish, annotated as Mate3-8, which form a distinct cluster separated from the tetrapod MATEs/Mates. Synteny analysis showed that zebrafish mate genes are orthologous to human MATEs. Gene expression analysis revealed that all the mate transcripts were constitutively and differentially expressed during embryonic development, followed by pronounced and tissue-specific expression in adults. Functional analyses were performed using transport activity assays with model substrates after heterologous overexpression of five zebrafish Mates in HEK293T cells. The results showed that zebrafish Mates interact with both physiological and xenobiotic substances but also substantially differ with respect to the interacting compounds and interaction strength in comparison to mammalian MATEs/Mates. Taken together, our data clearly indicate a potentially important role for zebrafish Mate transporters in zebrafish embryos and adults and provide a basis for detailed functional characterizations of single zebrafish Mate transporters.
authors.affiliation: Laboratory for Molecular Ecotoxicology, Division for Marine and Environmental Research, Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: Jovica
authors.initials: J
authors.lastname: Lončar
authors.affiliation: Laboratory for Molecular Ecotoxicology, Division for Marine and Environmental Research, Ruđer Bošković Institute, Zagreb, Croatia.|Oxford Institute for Radiation Oncology, University of Oxford, Oxford, England, United Kingdom.
authors.forename: Marta
authors.initials: M
authors.lastname: Popović
authors.affiliation: Institute of Molecular Systems Biology, ETH Zurich, Switzerland.
authors.forename: Petra
authors.initials: P
authors.lastname: Krznar
authors.affiliation: Laboratory for Molecular Ecotoxicology, Division for Marine and Environmental Research, Ruđer Bošković Institute, Zagreb, Croatia.|Sir William Dunn School of Pathology, University of Oxford, Oxford, England, United Kingdom.
authors.forename: Roko
authors.initials: R
authors.lastname: Zaja
authors.affiliation: Laboratory for Molecular Ecotoxicology, Division for Marine and Environmental Research, Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: Tvrtko
authors.initials: T
authors.lastname: Smital
mesh_terms: D000818:Animals; D003001:Cloning, Molecular; D005260:Female; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D027701:Organic Cation Transport Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*
chemical_list: D027701:Organic Cation Transport Proteins; C521869:SLC47A1 protein, human; D029961:Zebrafish Proteins