Direct binding of ligandin to uridine 5'-diphosphate glucuronosyltransferase 1A1.
OBJECTIVE
Bilirubin, a final degradation product of heme produced mainly in the spleen, is carried to the liver through its binding to albumin in the blood circulation. After its transport to hepatocytes, ligandin (glutathione S-transferase; GST) carries bilirubin to the endoplasmic reticulum (ER). uridine 5'-diphosphate-glucuronosyltransferase 1A1 (UGT1A1) glucuronidates bilirubin for solubilization in the ER.


METHODS
By GST pull-down and co-immunoprecipitation assays, GSTA2, a member of the alpha-class of GST, was observed to directly bind to UGT1A1 through the region present inside the ER.


RESULTS
GSTA2 was detected in the microsomal fraction together with the cytosolic fraction after hepatocyte fractionation.


CONCLUSIONS
These results strongly suggest that bilirubin is directly delivered to UGT1A1 from ligandin for glucuronidation.
Akizawa
Emi
E
Department of Applied Biological Science, Tokyo University of Science, Chiba, Japan.
Koiwai
Kotaro
K
Hayano
Takahide
T
Maezawa
So
S
Matsushita
Toyofumi
T
Koiwai
Osamu
O