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Titolo:
MOLECULAR CHARACTERISTICS OF MAMMALIAN AND INSECT AMINO-ACID TRANSPORTERS - IMPLICATIONS FOR AMINO-ACID HOMEOSTASIS
Autore:
CASTAGNA M; SHAYAKUL C; TROTTI D; SACCHI VF; HARVEY WR; HEDIGER MA;
Indirizzi:
BRIGHAM & WOMENS HOSP,DEPT MED,DIV RENAL BOSTON MA 02115 HARVARD UNIV,BRIGHAM & WOMENS HOSP,DEPT MED,DIV RENAL BOSTON MA 02115 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL BOSTON MA 02115 TEMPLE UNIV,DEPT BIOL PHILADELPHIA PA 19122 FAC FARM,IST FISIOL GEN & CHIM BIOL I-20134 MILAN ITALY
Titolo Testata:
Journal of Experimental Biology
fascicolo: 2, volume: 200, anno: 1997,
pagine: 269 - 286
SICI:
0022-0949(1997)200:2<269:MCOMAI>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
BRUSH-BORDER MEMBRANE; XENOPUS-LAEVIS OOCYTES; LARVAL MANDUCA-SEXTA; AFFINITY GLUTAMATE TRANSPORTER; SENSITIVE DOPAMINE TRANSPORTER; ISOLATED RAT HEPATOCYTES; NA+-DEPENDENT TRANSPORT; BRAIN GABA TRANSPORTER; L-PROLINE TRANSPORTER; CELL-SURFACE ANTIGEN;
Keywords:
AMINO ACID TRANSPORT; INTESTINE; KIDNEY; BRAIN; LEPIDOPTERAN INSECTS; NEUROTRANSMITTER; GLUTAMATE; GABA; CYSTINURIA;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
198
Recensione:
Indirizzi per estratti:
Citazione:
M. Castagna et al., "MOLECULAR CHARACTERISTICS OF MAMMALIAN AND INSECT AMINO-ACID TRANSPORTERS - IMPLICATIONS FOR AMINO-ACID HOMEOSTASIS", Journal of Experimental Biology, 200(2), 1997, pp. 269-286

Abstract

In mammalian cells, the uptake of amino acids is mediated by specialized, energy-dependent and passive transporters with overlapping substrate specificities, Most energy-dependent transporters are coupled either to the cotransport of Na+ or Cl- or to the countertransport of K+. Passive transporters are either facilitated transporters or channels. As a prelude to the molecular characterization of the different classes of transporters, we have isolated transporter cDNAs by expression-cloning with Xenopus laevis oocytes and we have characterized the clonedtransporters functionally by uptake studies into oocytes using radiolabelled substrates and by electrophysiology to determine substrate-evoked currents, Mammalian transporters investigated include the dibasic and neutral amino acid transport protein D2/NBAT (system b(0+)) and the Na+- and K+-dependent neuronal and epithelial high-affinity glutamate transporter EAAC1 (system X(AG)(-)). A detailed characterization of these proteins has provided new information on transport characteristics and mechanisms for coupling to different inorganic ions, This work has furthermore advanced our understanding of the roles these transporters play in amino acid homeostasis and in various pathologies, For example, in the central nervous system, glutamate transporters are critically important in maintaining the extracellular glutamate concentration below neurotoxic levels, and defects of the human D2 gene have beenshown to account for the formation of kidney stones in patients with cystinuria. Using similar approaches, we are investigating the molecular characteristics of K+-coupled amino acid transporters in the larvallepidopteran insect midgut. In the larval midgut, K+ is actively secreted into the lumen through the concerted action of an apical H+ V-ATPase and an apical K+/2H(+) antiporter, thereby providing the driving force for absorption of amino acids, In vivo, the uptake occurs at extremely high pH (pH10) and is driven by a large potential difference (approximately -200 mV). Studies with brush-border membrane vesicles haveshown that there are several transport systems in the larval intestine with distinct amino acid and cation specificities, In addition to K+, Na+ can also be coupled to amino acid uptake at lower pH, but the Na/K+ ratio of the hemolymph is so low that K+ is probably the major coupling ion in vivo. The neutral amino acid transport system of larval midgut has been studied most extensively, Apart from its cation selectivity, it appears to be related to the amino acid transport system B previously characterized in vertebrate epithelial cells, Both systems have a broad substrate range which excludes 2-(methylamino)-isobutyric acid, an amino acid analog accepted by the mammalian Na+-coupled system A. In order to gain insights into the K+-coupling mechanism and intoamino acid and K+ homeostasis in insects, current studies are designed to delineate the molecular characteristics of these insect transporters. Recent data showed that injection of mRNA prepared from the midgut of Manduca sexta into Xenopus laevis oocytes induced a 1.5- to 2.5-fold stimulation of the Na+-dependent uptake of both leucine and phenylalanine (0.2 mmol l(-1), pH 8). The molecular cloning of these transporters is now in progress, Knowledge of their unique molecular properties could be exploited in the future to control disease vectors and insect pests.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 21:03:09