title: Arginine transport in human erythroid cells: discrimination of CAT1 and 4F2hc/y+LAT2 roles.
abstract: Since arginine metabolites, such as nitric oxide and polyamines, influence the expression of genes involved in erythroid differentiation, the transport of the cationic amino acid may play an important role in erythroid cells. However, available data only concern the presence in these cells of CAT1 transporter (system y(+)), while no information exists on the role of the heterodimeric transporters of system y(+)L (4F2hc/y(+)LAT1 and 4F2hc/y(+)LAT2) which operates transmembrane arginine fluxes cis-inhibited by neutral amino acids in the presence of sodium. Using erythroleukemia K562 cells and normal erythroid precursors, we demonstrate here that arginine transport in human erythroid cells is due to the additive contributions of a leucine-sensitive and leucine-insensitive component. In both cell types, leucine inhibition of arginine influx is much less evident in the absence of sodium, a hallmark of system y(+)L. In K562 cells, N-ethylmaleimide, a known inhibitor of CAT transporters (system y(+)), suppresses only a fraction of arginine influx corresponding to leucine-insensitive uptake. Moreover, in Xenopus oocytes coexpressing 4F2hc and y(+)LAT2, leucine exerts a marked inhibition of arginine transport, partially dependent on sodium, while no inhibition is seen in oocytes expressing CAT1. Lastly, silencing of SLC7A6, the gene for y(+)LAT2, lowers arginine transport and doubles the intracellular content of the cationic amino acid in K562 cells. We conclude that arginine transport in human erythroid cells is due to both system y(+) (CAT1 transporter) and system y(+)L (4F2hc/y(+)LAT2 isoform), which mainly contribute, respectively, to the influx and to the efflux of the cationic amino acid.
authors: Unit of General and Clinical Pathology, Department of Experimental Medicine, University of Parma, Via Volturno, 39-43125, Parma, Italy.
authors: Bianca Maria
authors: BM
authors: Rotoli
authors: Ellen I
authors: EI
authors: Closs
authors: Amelia
authors: A
authors: Barilli
authors: Rossana
authors: R
authors: Visigalli
authors: Alexandra
authors: A
authors: Simon
authors: Alice
authors: A
authors: Habermeier
authors: Nicoletta
authors: N
authors: Bianchi
authors: Roberto
authors: R
authors: Gambari
authors: Gian C
authors: GC
authors: Gazzola
authors: Ovidio
authors: O
authors: Bussolati
authors: Valeria
authors: V
authors: Dall'Asta
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D027182:Amino Acid Transport System y+ / Q000378:metabolism; D026923:Amino Acid Transport Systems, Basic / Q000502:physiology; D000818:Animals; D001120:Arginine / Q000378:metabolism; D027201:Cationic Amino Acid Transporter 1 / Q000378:metabolism; D015672:Erythroid Precursor Cells / Q000378:metabolism*; D027282:Fusion Regulatory Protein 1, Heavy Chain / Q000502:physiology*; D020868:Gene Silencing; D006801:Humans; D020014:K562 Cells; D027283:Large Neutral Amino Acid-Transporter 1 / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D027182:Amino Acid Transport System y+; D026923:Amino Acid Transport Systems, Basic; D027201:Cationic Amino Acid Transporter 1; D027282:Fusion Regulatory Protein 1, Heavy Chain; C419196:LAT2 protein, human; D027283:Large Neutral Amino Acid-Transporter 1; C545989:SLC3A2 protein, human; C469951:SLC7A6 protein, human; D001120:Arginine