Rheogenic amino acid transport by Drosophila CG4991 of the Amino Acid Auxin Permease (AAAP) transporter family

Abstract

To increase our understanding of how differences in structure determine membrane transporter function, a member of the Amino Acid Auxin Permease (AAAP) family from Drosophila was investigated. CG4991 is an orthologue of the mammalian SLC36 proton‐coupled amino acid transporter family showing 32% identity in amino acid sequence with human PAT1 (SLC36A1). Transport characteristics were compared with those for mammalian PAT1 and PAT2 (SLC36A2). CG4991 was characterised functionally, following expression in Xenopus laevis oocytes, by radiotracer uptake, competition experiments, and measurements of rheogenic transport using the two‐electrode voltage‐clamp technique. As observed with mammalian PAT1 and PAT2, CG4991 functions as a pH‐dependent dipolar amino acid transporter with optimal taurine uptake at extracellular pH 5.0–5.5. Taurine uptake was independent of sodium at both pH 5.5 and 7.5. CG4991 demonstrates both similarities and differences in substrate selectivity when compared to PAT1 and PAT2. For example, CG4991, like PAT1, transports proline, glycine, beta‐alanine, betaine and MeAIB but unlike PAT1 transports serine. In conclusion, the commonality of CG4991, PAT1 and PAT2 transporter characteristics, suggests conservation of function despite relatively low levels of sequence identity. Supported by the Medical Research Council (MRC).