title: ABCB- and ABCC-type transporters confer multixenobiotic resistance and form an environment-tissue barrier in bivalve gills.
abstract: Aquatic organisms and, in particular, filter feeders, such as mussels, are continuously exposed to toxicants dissolved in the water and, presumably, require adaptations to avoid the detrimental effects from such chemicals. Previous work indicates that activity of ATP-binding cassette (ABC) transporters protects mussels against toxicants, but the nature of these transporters and the structural basis of protection are not known. Here we meld studies on transporter function, gene expression, and localization of transporter protein in mussel gill tissue and show activity and expression of two xenobiotic transporter types in the gills, where they provide an effective structural barrier against chemicals. Activity of ABCB/MDR/P-glycoprotein and ABCC/MRP-type transporters was indicated by sensitivity of efflux of the test substrate calcein-AM to the ABCB inhibitor PSC-833 and the ABCC inhibitor MK-571. This activity profile is supported by our cloning of the complete sequence of two ABC transporter types from RNA in mussel tissue with a high degree of identity to transporters from the ABCB and ABCC subfamilies. Overall identity of the amino acid sequences with corresponding homologs from other organisms was 38-50% (ABCB) and 27-44% (ABCC). C219 antibody staining specific for ABCB revealed that this transporter was restricted to cells in the gill filaments with direct exposure to water flow. Taken together, our data demonstrate that ABC transporters form an active, physiological barrier at the tissue-environment interface in mussel gills, providing protection against environmental xenotoxicants.
authors.affiliation: Department of Cell Toxicology, UFZ, Helmholtz Centre for Environmental Research, Permoserstrasse 15, Leipzig, Germany. till.luckenbach@ufz.de
authors.forename: Till
authors.initials: T
authors.lastname: Luckenbach
authors.forename: David
authors.initials: D
authors.lastname: Epel
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D003524:Cyclosporins / Q000494:pharmacology; D004781:Environmental Exposure / Q000517:prevention & control*; D005880:Gills / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D049878:Mytilus / Q000187:drug effects / Q000502:physiology*; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D015262:Xenobiotics / Q000009:adverse effects*
chemical_list: D018528:ATP-Binding Cassette Transporters; D003524:Cyclosporins; D011422:Propionates; D011804:Quinolines; D015262:Xenobiotics; C059141:verlukast; C070272:valspodar