title: Molecular characterization of the first aromatic nutrient transporter from the sodium neurotransmitter symporter family.
abstract: Nutrient amino acid transporters (NATs, subfamily of sodium neurotransmitter symporter family SNF, a.k.a. SLC6) represent a set of phylogenetically and functionally related transport proteins, which perform intracellular absorption of neutral, predominantly essential amino acids. Functions of NATs appear to be critical for the development and survival in organisms. However, mechanisms of specific and synergetic action of various NAT members in the amino acid transport network are virtually unexplored. A new transporter, agNAT8, was cloned from the malaria vector mosquito Anopheles gambiae (SS). Upon heterologous expression in Xenopus oocytes it performs high-capacity, sodium-coupled (2:1) uptake of nutrients with a strong preference for aromatic catechol-branched substrates, especially phenylalanine and its derivatives tyrosine and L-DOPA, but not catecholamines. It represents a previously unknown SNF phenotype, and also appears to be the first sodium-dependent B(0) type transporter with a narrow selectivity for essential precursors of catecholamine synthesis pathways. It is strongly and specifically transcribed in absorptive and secretory parts of the larval alimentary canal and specific populations of central and peripheral neurons of visual-, chemo- and mechano-sensory afferents. We have identified a new SNF transporter with previously unknown phenotype and showed its important role in the accumulation and redistribution of aromatic substrates. Our results strongly suggest that agNAT8 is an important, if not the major, provider of an essential catechol group in the synthesis of catecholamines for neurochemical signaling as well as ecdysozoan melanization and sclerotization pathways, which may include cuticle hardening/coloring, wound curing, oogenesis, immune responses and melanization of pathogens.
authors.affiliation: The Whitney Laboratory for Marine Bioscience, University of Florida, 9505 Ocean Shore Blvd., St Augustine, FL 32080, USA.
authors.forename: Ella A
authors.initials: EA
authors.lastname: Meleshkevitch
authors.forename: Poincyane
authors.initials: P
authors.lastname: Assis-Nascimento
authors.forename: Lyudmila B
authors.initials: LB
authors.lastname: Popova
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Miller
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Kohn
authors.forename: Elizabeth N
authors.initials: EN
authors.lastname: Phung
authors.forename: Anita
authors.initials: A
authors.lastname: Mandal
authors.forename: William R
authors.initials: WR
authors.lastname: Harvey
authors.forename: Dmitri Y
authors.initials: DY
authors.lastname: Boudko
mesh_terms: D000595:Amino Acid Sequence; D026905:Amino Acid Transport Systems / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D024322:Amino Acids, Aromatic / Q000378:metabolism*; D000818:Animals; D000852:Anopheles / Q000033:anatomy & histology / Q000235:genetics / Q000378:metabolism*; D002395:Catecholamines / Q000096:biosynthesis; D002396:Catechols / Q000378:metabolism; D003001:Cloning, Molecular; D004553:Electric Conductivity; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D010802:Phylogeny; D050480:Plasma Membrane Neurotransmitter Transport Proteins / Q000235:genetics; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction / Q000235:genetics; D014981:Xenopus
chemical_list: D026905:Amino Acid Transport Systems; D024322:Amino Acids, Aromatic; D002395:Catecholamines; D002396:Catechols; D019476:Insect Proteins; D050480:Plasma Membrane Neurotransmitter Transport Proteins; D012333:RNA, Messenger; C034221:catechol