The Drosophila ATP-Binding Cassette transporter gene dMRP is related to the human Multidrug Resistance-associated Protein (MRP) family and functions as a xenobiotic transporter

Thesis (Ph.D.)--University of Hawaii at Manoa, 2008.Transport proteins provide essential cellular functions for archaea, bacteria and eukaryotes. Of the over 550 classified transporter families the ATP-Binding Cassette (ABC) Superfamily is one of the largest. The ABC Transporter Superfamily is divided into eight subfamilies designated A thru H. Members of this superfamily are involved in the transport of a variety of physiologically important substrates including ions, sugars, amino acids, vitamins, peptides, lipids and hormones. ABC transporters are also involved in diverse cellular processes such as lipid trafficking, antigen processing, nutrient uptake, and xenobiotic detoxification. Mutations in several ABC transporters result in various genetic diseases, while overexpression of certain key members of the ABCB/Multidrug Resistance (MDR) and ABCC/Multidrug Resistance-associated Protein (MRP) subfamilies can lead to the development of cellular multixenobiotic resistance. Phylogenetic analysis of the Drosophila genome has identified the Drosophila MRP (dMRP) gene as orthologous to three human genes capable of conferring xenobiotic resistance, the human ABCC1/MRP1, ABCC2/MRP2 and ABCC3/MRP3 genes. In vivo and in vitro experiments have shown that the dMRP gene is ubiquitously expressed throughout Drosophila development and established the dMRP gene as a functional ABC transporter. In vivo and in vitro pesticide assays indicated that dMRP is a pesticide-inducible xenobiotic transporter involved in pesticide metabolism.Includes bibliographical references (leaves 209-240).Also available by subscription via World Wide Web240 leaves, bound 29 c