| Cloning and functional expression of the first eukaryotic Na+-tryptophan symporter, AgNAT6. | |
| | |
MedLine Citation:
|
PMID: 19411550 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
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: 2012-04-24 |
Medline Journal Info:
|
Nlm Unique ID: 0243705 Medline TA: J Exp Biol Country: England |
Other Details:
|
Languages: eng Pagination: 1559-67 Citation Subset: IM |
Affiliation:
|
Department of Physiology and Biophysics, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amino Acid Sequence Animals Anopheles gambiae / genetics, metabolism* Cloning, Molecular* Gene Expression Regulation / physiology Larva / metabolism Molecular Sequence Data Phylogeny Sodium / metabolism* Symporters / chemistry, genetics, metabolism* Tryptophan / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
|
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 |
| Chemical | |
Reg. No./Substance:
|
0/Symporters; 73-22-3/Tryptophan; 7440-23-5/Sodium |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The role of insulin and glucose in goose primary hepatocyte triglyceride accumulation.
Next Document: Eye movements of laterally eyed birds are not independent.