The invertebrate B 0 system transporter, D. melanogaster NAT1, has unique d-amino acid affinity and mediates gut and brain functions

Abstract

The CG3252 gene product, DmNAT1, represents the first Nutrient Amino acid Transporter cloned from Drosophila. It absorbs a broader set of neutral amino acids versus earlier characterized insect NATs and mammalian NATs-B 0 system transporters from the Sodium Neurotransmitter symporter Family (SNF, a.k.a. solute carrier family 6, SLC6). In addition to B 0-specific l-substrates, DmNAT1 equally or more effectively transports d-amino acids with sub-millimolar affinities and 1:1 sodium:amino acid transport stoichiometry. DmNAT1 is strongly transcribed in the absorptive and secretory regions of the larval alimentary canal and larval brain, revealing its roles in the primary absorption and redistribution of large neutral l-amino acids as well as corresponding d-isomers. The absorption of d-amino acids via DmNAT1 may benefit the acquisition of fermented and symbiotic products, and may support the unique capacity of fruit fly larvae to utilize a diet with substitution of essential amino acids by d-isomers. It also suggests a remarkable adaptive plasticity of NAT-SLC6 mechanisms via alterations of a few identifiable sites in the substrate-binding pocket. The strong transcription in the brain suggests roles for DmNAT1 in neuronal nutrition and clearance of l-neutral amino acids from the fly brain. In addition, neuronal DmNAT1 may absorb synaptic d-serine and modulate NMDA receptor-coupled signal transduction. The characterization of the first invertebrate B 0-like transporter extends the biological roles of the SLC6 family, revealing adaptations for the absorption of d-isomers of the essential amino acids. These findings suggest that some members of the NAT-SLC6 subfamily are evolving specific properties which contribute to nutrient symbiotic relationships and neuronal functions.