Expression of the urate transporter/channel is developmentally regulated in human kidneys.
Recombinant protein prepared from cDNA cloned from rat kidney and its human homolog function as urate transporter/channels in lipid bilayers. Using the antibody (anti-uricase) that detected the rat cDNA clone, we now demonstrate that normal human kidneys contain an immunoreactive protein of identical size to that in rat kidney (36-37 kDa), presumably the human urate transporter/channel (hUAT). The amount of hUAT in kidney homogenates increases progressively from 13 wk of gestation to the early postnatal period. During gestation, hUAT expression is confined to the cytoplasm of proximal tubules of Stage III and/or IV nephrons. However, at 1 yr of age hUAT is primarily located subapically and within brush borders of proximal tubules. Xenopus laevis oocytes and differentiated A6 cells injected with cRNA and transfected with cDNA of hUAT, respectively, demonstrated a similar pattern: hUAT is not detected in oocytes but is abundantly expressed in cytoplasm and plasma membranes of A6 cells. These data imply that different developmental factors regulate the initiation of cytoplasmic hUAT expression and subsequent insertion into human proximal tubule brush-border membranes.
Hyink
D P
DP
Division of Nephrology, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
Rappoport
J Z
JZ
Wilson
P D
PD
Abramson
R G
RG
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D007668:Kidney / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*; D007672:Kidney Cortex / Q000737:chemistry / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000648:ultrastructure; D008871:Microvilli / Q000201:enzymology; D008875:Middle Aged; D008969:Molecular Sequence Data; D009399:Nephrons / Q000737:chemistry / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism / Q000648:ultrastructure; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014982:Xenopus laevis
D002352:Carrier Proteins; C491242:Lgals9 protein, rat; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D011994:Recombinant Proteins; C491241:SLC22A12 protein, human; C103862:urate transporter