We have previously reported that the rat hepatic lectin-1 (RHL-1) subunit o
f rat asialoglycoprotein receptor (ASGPr), the endocytic receptor found ore
the basolateral surface of hepatocytes, was expressed in rat thyroid tissu
e and localized on the apical surface of polarized rat thyroid FRT cells. H
ere we show that PC Cl3 cells, a differentiated rat thyroid cell line, boun
d thyroglobulin (Tg) via ASGPr. In fact, both the bacterial recombinant car
bohydrate recognition domain of RHL-1 (rCRD(RHL-1)) and the anti-rCRD(RHL-1
) antibody markedly inhibited I-125-Tg binding to the cell surface of PC Cl
3 cells. Ligand blot assays with deglycosylated Tg show that the rCRD(RHL-1
), was able to interact with Tg even after remotion of sugars. The region o
f Tg involved in the binding to RHL-1 was investigated by ligand blot assay
s with biotinylated rCRD(RHL-1) on thermolysin-digested native and desialat
ed rat thyroglobulin. It is shown that the rCRD(RHL-1), specifically recogn
ized a thyroglobulin fragment with an apparent M-r of 68,000, corresponding
to the amino-terminal part of the molecule. To our knowledge, this is the
first report that attributes to the amino-terminal portion of Tg molecule,
containing its earliest and major hormonogenic site, the function of bindin
g to a cell surface receptor of the thyroid. Moreover, we show that oligosa
ccharides are not the only molecular signals for binding to RHL-1, but amin
o acidic determinants could also play a role, (C) 2000 Academic Press.