title: Localization, regulation, and substrate transport properties of Bpt1p, a Saccharomyces cerevisiae MRP-type ABC transporter.
abstract: Saccharomyces cerevisiae Bpt1p is an ATP-binding cassette (ABC) protein that belongs to the MRP subfamily and is a close homologue of the glutathione conjugate (GS conjugate) transporter Ycf1p. The function of Bpt1p has previously been evaluated only in vitro, by using nonphysiological substrates. In the present study we examined the localization, regulation, and transport properties of Bpt1p in vivo, as well as its capacity to transport a set of prototypical MRP substrates in vitro. Our results show that Bpt1p, like Ycf1p, localizes to the yeast vacuolar membrane, plays a role in cadmium detoxification and ade2 pigmentation in vivo, and can participate in the transport of GS conjugates and glucuronate conjugates, as well as free glutathione, in vitro. However, in all of these cases the contribution of Bpt1p is substantially less than that of Ycf1p. In addition, the expression patterns of YCF1 and BPT1 differ significantly. Whereas YCF1 expression is markedly increased by cadmium, adenine limitation in an ade2 strain, or overexpression of the stress-responsive transcription factor Yap1p, BPT1 expression is only modestly affected under these conditions. Thus, although the functional capabilities of Bpt1p and Ycf1p overlap, their differences in regulation and substrate preference imply that they contribute to cellular detoxification processes in different ways.
authors.affiliation: Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 USA.
authors.forename: Kailash Gulshan
authors.initials: KG
authors.lastname: Sharma
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Mason
authors.forename: Guosheng
authors.initials: G
authors.lastname: Liu
authors.forename: Philip A
authors.initials: PA
authors.lastname: Rea
authors.forename: Anand K
authors.initials: AK
authors.lastname: Bachhawat
authors.forename: Susan
authors.initials: S
authors.lastname: Michaelis
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D001693:Biological Transport, Active; D002104:Cadmium / Q000633:toxicity; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005800:Genes, Fungal; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014617:Vacuoles / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D002104:Cadmium; D005656:Fungal Proteins; D005978:Glutathione; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D029701:Saccharomyces cerevisiae Proteins; C089179:YCF1 protein, S cerevisiae; C421109:multidrug resistance-associated protein 1