Identification of LAT4, a novel amino acid transporter with system L activity.
System L amino acid transporters mediate the movement of bulky neutral amino acids across cell membranes. Until now three proteins that induce system L activity have been identified: LAT1, LAT2, and LAT3. The former two proteins belong to the solute carrier family 7 (SLC7), whereas the latter belongs to SLC43. In the present study we present a new cDNA, designated LAT4, which also mediates system L activity when expressed in Xenopus laevis oocytes. Human LAT4 exhibits 57% identity to human LAT3. Like LAT3, the amino acid transport activity induced by LAT4 is sodium-, chloride- and pH-independent, is not trans-stimulated, and shows two kinetic components. The low affinity component of LAT4 induced activity is sensitive to the sulfhydryl-specific reagent N-ethylmaleimide but not that with high affinity. Mutation in LAT4 of the SLC43 conserved serine 297 to alanine abolishes sensitivity to N-ethylmaleimide. LAT4 activity is detected at the basolateral membrane of PCT kidney cells. In situ hybridization experiments show that LAT4 mRNA is restricted to the epithelial cells of the distal tubule and the collecting duct in the kidney. In the intestine, LAT4 is mainly present in the cells of the crypt.
Bodoy
Susanna
S
Department of Biochemistry and Molecular Biology, University of Barcelona, Avda Diagonal 645, Barcelona E-08028, Spain.
Martín
Lorena
L
Zorzano
Antonio
A
Palacín
Manuel
M
Estévez
Raúl
R
Bertran
Joan
J
D000595:Amino Acid Sequence; D027062:Amino Acid Transport System L / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D026923:Amino Acid Transport Systems, Basic / Q000032:analysis / Q000235:genetics / Q000502:physiology; D000818:Animals; D005033:Ethylmaleimide / Q000494:pharmacology; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D007422:Intestines / Q000737:chemistry; D007668:Kidney / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D010649:Phenylalanine / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D014982:Xenopus laevis
D027062:Amino Acid Transport System L; D026923:Amino Acid Transport Systems, Basic; D012333:RNA, Messenger; C469951:SLC7A6 protein, human; D010649:Phenylalanine; D005033:Ethylmaleimide