Insights into the transport side of the human SLC38A9 transceptor.

Détails

ID Serval
serval:BIB_5CE1146D9723
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Insights into the transport side of the human SLC38A9 transceptor.
Périodique
Biochimica et biophysica acta. Biomembranes
Auteur(s)
Scalise M., Galluccio M., Pochini L., Cosco J., Trotta M., Rebsamen M., Superti-Furga G., Indiveri C.
ISSN
1879-2642 (Electronic)
ISSN-L
0005-2736
Statut éditorial
Publié
Date de publication
01/09/2019
Peer-reviewed
Oui
Volume
1861
Numéro
9
Pages
1558-1567
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The lysosomal amino acid transporter SLC38A9 is referred to as transceptor, i.e. a transporter with a receptor function. The protein is responsible for coupling amino acid transport across the lysosomal membrane according to the substrate availability to mTORC1 signal transduction. This process allows cells to sense amino acid level responding to growth stimuli in physiological and pathological conditions triggering mTOR regulation. The main substrates underlying this function are glutamine and arginine. The functional and kinetic characterization of glutamine and arginine transport was performed using human SLC38A9 produced in E. coli, purified by affinity chromatography and reconstituted in liposomes. A cooperative behaviour for the wild type protein was revealed for both the substrates. A novel Na <sup>+</sup> binding site, namely T453, was described by combined approaches of bioinformatics, site-directed mutagenesis and transport assay. Stimulation by cholesterol of glutamine and arginine transport was observed. The biological function of SLC38A9 relies on the interaction between its N-terminus and components of the mTOR complex; a deletion mutant of the N-terminus tail was produced and transport of glutamine was assayed revealing that this portion does not play any role in the intrinsic transport function of the human SLC38A9. Different features for glutamine and arginine transport were revealed: human SLC38A9 is competent for glutamine efflux, while that of arginine is negligible. In line with these results, imposed ∆pH stimulated glutamine, not arginine transport. Arginine plays, on the contrary, a modulatory function and is able to stimulate glutamine efflux. Interestingly, reciprocal inhibition experiments also supported by bioinformatics, suggested that glutamine and arginine may bind to different sites in the human SLC38A9 transporter.
Mots-clé
Amino Acid Transport Systems/chemistry, Amino Acid Transport Systems/genetics, Amino Acid Transport Systems/metabolism, Amino Acid Transport Systems/physiology, Amino Acids/metabolism, Arginine/metabolism, Binding Sites, Biological Transport, Cholesterol/metabolism, Glutamine/metabolism, Humans, Ion Transport, Kinetics, Lysosomes/metabolism, Signal Transduction, TOR Serine-Threonine Kinases/metabolism, Cholesterol, Glutamine, Proteoliposomes, Transceptor, hSLC38A9, mTOR
Pubmed
Web of science
Création de la notice
11/08/2020 17:06
Dernière modification de la notice
13/08/2020 6:26
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