Reabsorption of neutral amino acids mediated by amino acid transporter LAT2 and TAT1 in the basolateral membrane of proximal tubule.
In order to understand the renal reabsorption mechanism of neutral amino acids via amino acid transporters, we have isolated human L-type amino acid transporter 2 (hLAT2) and human T-type amino acid transporter 1 (hTAT1) in human, then, we have examined and compared the gene structures, the functional characterizations and the localization in human kidney. Northern blot analysis showed that hLAT2 mRNA was expressed at high levels in the heart, brain, placenta, kidney, spleen, prostate, testis, ovary, lymph node and the fetal liver. The hTAT1 mRNA was detected at high levels in the heart, placenta, liver, skeletal muscle, kidney, pancreas, spleen, thymus and prostate. Immunohistochemical analysis on the human kidney revealed that the hLAT2 and hTAT1 proteins coexist in the basolateral membrane of the renal proximal tubules. The hLAT2 transports all neutral amino acids and hTAT1 transports aromatic amino acids. The basolateral location of the hLAT2 and hTAT1 proteins in the renal proximal tubule as well as the amino acid transport activity of hLAT2 and hTAT1 suggests that these transporters contribute to the renal reabsorption of neutral and aromatic amino acids in the basolateral domain of epithelial proximal tubule cells, respectively. Therefore, LAT2 and TAT1 play essential roles in the reabsorption of neutral amino acids from the epithelial cells to the blood stream in the kidney. Because LAT2 and TAT1 are essential to the efficient absorption of neutral amino acids from the kidney, their defects might be involved in the pathogenesis of disorders caused by a disruption in amino acid absorption such as blue diaper syndrome.
Park
Sun Young
SY
Department of Pediatrics, Kwangju Christian Hospital, Gwangju 503-715, Korea.
Kim
Jong-Keun
JK
Kim
In Jin
IJ
Choi
Bong Kyu
BK
Jung
Kyu Yong
KY
Lee
Seoul
S
Park
Kyung Jin
KJ
Chairoungdua
Arthit
A
Kanai
Yoshikatsu
Y
Endou
Hitoshi
H
Kim
Do Kyung
DK
D000042:Absorption; D000595:Amino Acid Sequence; D027182:Amino Acid Transport System y+ / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D026921:Amino Acid Transport Systems, Neutral / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D021542:Amino Acids, Neutral / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D015152:Blotting, Northern; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D003001:Cloning, Molecular; D027301:Fusion Regulatory Protein 1, Light Chains / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D014982:Xenopus laevis
D027182:Amino Acid Transport System y+; D026921:Amino Acid Transport Systems, Neutral; D021542:Amino Acids, Neutral; D027301:Fusion Regulatory Protein 1, Light Chains; C498964:SLC16A10 protein, human; C420646:SLC7A8 protein, human