A new member of the cationic amino acid transporter family is preferentially expressed in adult mouse brain.
We have isolated and characterized a novel member (CAT3) of the cationic amino acid transporter (CAT) family. In oocyte injection assays, CAT3 cRNA exhibited a saturable, sodium ion-independent transport activity with high affinity for L-arginine and L-lysine (Km = 40-60 and 115-165 microM, respectively). Transport of L-arginine was effectively competed only by cationic amino acids in L-form: arginine, lysine, ornithine, and 2,4-diamino-n-butyric acid but not by 2,3-diaminopropionic acid. The presence of L-arginine in the incubation medium stimulated the efflux rate of L-arginine, indicating that CAT3 is subject to trans-stimulation. All these results are consistent with the idea that CAT3, along with CAT1 and CAT2, constitutes the transport activity originally assigned to system y+. Like CAT2, but unlike CAT1, the expression of CAT3 is regulated in a highly tissue-specific manner; when various adult tissues were examined, significant levels of CAT3 transcript were detectable only in brain. In situ hybridization on brain sections revealed that CAT3 transcripts were localized predominantly along the midbrain-thalamus-hypothalamus axis, whereas neither CAT1 nor CAT2 transcripts demonstrated a similar localization. In contrast to its highly localized expression during the primitive streak stage and in the adult stage, CAT3 expression was detected more widely in 13.5 day post-coitum mouse embryos.
Ito
K
K
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, USA. kito@acs.ucalgary.ca
Groudine
M
M
D000595:Amino Acid Sequence; D026923:Amino Acid Transport Systems, Basic; D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary; D005333:Fetus / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins