Ancestry and progeny of nutrient amino acid transporters

Abstract

The biosynthesis of structural and signaling molecules depends on intracellular concentrations of essential amino acids, which are maintained by a specific system of plasma membrane transporters. We identify a unique population of nutrient amino acid transporters (NATs) within the sodium-neurotransmitter symporter family and have characterized a member of the NAT subfamily from the larval midgut of the Yellow Fever vector mosquito, Aedes aegypti (aeAAT1, AAR08269), which primarily supplies phenylalanine, an essential substrate for the synthesis of neuronal and cuticular catecholamines. Further analysis suggests that NATs constitute a comprehensive transport metabolon for the epithelial uptake and redistribution of essential amino acids including precursors of several neurotransmitters. In contrast to the highly conserved subfamily of orthologous neurotransmitter transporters, lineagespecific, paralogous NATs undergo rapid gene multiplication͞ substitution that enables a high degree of evolutionary plasticity of nutrient amino acid uptake mechanisms and facilitates environmental and nutrient adaptations of organisms. These findings provide a unique model for understanding the molecular mechanisms, physiology, and evolution of amino acid and neurotransmitter transport systems and imply that monoamine and GABA transporters evolved by selection and conservation of earlier neuronal NATs.

Identification of a chloride ion binding site in Na + /Cl − -dependent transporters

“…Interestingly, N286LeuT is replaced by Asp in several transporters from insects (SI Fig. 5), which are generally Cl Ϫ -independent (2,21). This observation will be discussed in more detail below.…”

“…Members of this transporter family are responsible for uptake of neurotransmitters, such as glycine, ␥-amino butyric acid, serotonin, dopamine, and norepinephrine, from the synaptic cleft (1). NSS transporters selective for other amino acids have been found to be involved in metabolism, for example, in the larval midgut of the yellow fever vector mosquito (2). Consistent with these important functions, mutations in NSS transporters have been implicated in psychological and digestive disorders, including schizophrenia (3) and Hartnup disorder (4).…”

Comparative sequence analysis and tissue localization of members of the SLC6 family of transporters in adultDrosophila melanogaster

“…Our phylogenetic analysis identified a number of predicted genes that help define the novel insect amino acid transporter (IAAT) subfamily (Boudko et al, 2005), which to date is represented only in insects. Predicted sequences from Drosophila melanogaster (DmCG1698, DmCG3252, DmCG4476, DmCG8850, DmCG15088 and DmCG15279) and Anopheles gambie (AgCP10401, AgCP10412, AgCP10503 and AgCP10610) are clearly related to the Manduca sexta transporters KAAT1 (Castagna et al, 1998) and CAATCH1 (Feldman et al, 2000), which are competent to transport substrate amino acids using either K + or Na + as the driving ion.…”

“…For example, DmIne and AgCP4566 do not segregate nicely into a recognized subfamily. DmIne mediates a response to hypertonic solutions (Chiu et al, 2000) and has been proposed to comprise its own subfamily (Boudko et al, 2005). Other sequences, including a number of orphan transporters from C. elegans, vertebrate NTT-5 and putative Drosophila transporters (DmBlot, DmCG8291, DmCG13793, DmCG13794, DmCG13795 and DmCG33296) make up a loose assemblage of outliers, which do not appear to be affiliated with defined subfamilies.…”

“…Phylogenetic analysis revealed that these Drosophila SLC6 transporters segregated into four of the five previously recognized SLC6 subfamilies (Nelson, 1998) and helped to define a sixth subfamily, the insect amino acid transporters (IAAT) (Soragna et al, 2004;Boudko et al, 2005). Using in situ hybridization, we focused on localizing SLC6 transporters in the CNS of adult flies.…”