Document Detail

Cloning and functional expression of the first eukaryotic Na+-tryptophan symporter, AgNAT6.
MedLine Citation:
PMID:  19411550     Owner:  NLM     Status:  MEDLINE    
The nutrient amino acid transporter (NAT) subfamily of the neurotransmitter sodium symporter family (NSS, also known as the solute carrier family 6, SLC6) represents transport mechanisms with putative synergistic roles in the absorption of essential and conditionally essential neutral amino acids. It includes a large paralogous expansion of insect-specific genes, with seven genes from the genome of the malaria mosquito, Anopheles gambiae. One of the An. gambiae NATs, AgNAT8, was cloned, functionally expressed and characterized in X. laevis oocytes as a cation-coupled symporter of aromatic amino acids, preferably l-phenylalanine, l-tyrosine and l-DOPA. To explore an evolutionary trend of NAT-SLC6 phenotypes, we have cloned and characterized AgNAT6, which represents a counterpart of AgNAT8 descending from a recent gene duplication (53.1% pairwise sequence identity). In contrast to AgNAT8, which preferably mediates the absorption of phenol-branched substrates, AgNAT6 mediates the absorption of indole-branched substrates with highest apparent affinity to tryptophan (K(0.5)(Trp)=1.3 micromol l(-1) vs K(0.5)(Phe)=430 micromol l(-1)) and [2 or 1 Na(+) or K(+)]:[aromatic substrate] stoichiometry. AgNAT6 is highly transcribed in absorptive and secretory regions of the alimentary canal and specific neuronal structures, including the neuropile of ventral ganglia and sensory afferents. The alignment of AgNATs and LeuT(Aa), a bacterial NAT with a resolved 3D structure, reveals three amino acid differences in the substrate-binding pocket that may be responsible for the indole- vs phenol-branch selectivity of AgNAT6 vs AgNAT8. The identification of transporters with a narrow selectivity for essential amino acids suggests that basal expansions in the SLC6 family involved duplication and retention of NATs, improving the absorption and distribution of under-represented essential amino acids and related metabolites. The identified physiological and expression profiles suggest unique roles of AgNAT6 in the active absorption of indole-branched substrates that are used in the synthesis of the neurotransmitter serotonin as well as the key circadian hormone and potent free-radical scavenger melatonin.
Ella A Meleshkevitch; Marvin Robinson; Lyudmila B Popova; Melissa M Miller; William R Harvey; Dmitri Y Boudko
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The Journal of experimental biology     Volume:  212     ISSN:  0022-0949     ISO Abbreviation:  J. Exp. Biol.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-04     Completed Date:  2009-07-24     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  0243705     Medline TA:  J Exp Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1559-67     Citation Subset:  IM    
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MeSH Terms
Amino Acid Sequence
Anopheles gambiae / genetics,  metabolism*
Cloning, Molecular*
Gene Expression Regulation / physiology
Larva / metabolism
Molecular Sequence Data
Sodium / metabolism*
Symporters / chemistry,  genetics,  metabolism*
Tryptophan / metabolism*
Grant Support
R01 AI-030464/AI/NIAID NIH HHS; R01 AI030464/AI/NIAID NIH HHS; R01 AI030464-17/AI/NIAID NIH HHS; R56 AI030464/AI/NIAID NIH HHS; R56 AI030464-18/AI/NIAID NIH HHS
Reg. No./Substance:
0/Symporters; 8DUH1N11BX/Tryptophan; 9NEZ333N27/Sodium

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