Περίληψη:
After its endocytosis from the colloid, some thyroglobulin (Tg) is
transcytosed intact across thyrocytes, accounting in part for its
presence in the circulation. We previously showed that megalin (gp330),
an endocytic Tg receptor, mediates apical to basolateral Tg
transcytosis. Here we investigated whether a portion of megalin remains
combined with Tg after its transcytosis, using studies with cultured
thyroid cells and in, vivo observations.
FRTL-5 cells, a rat thyroid cell line, cultured on filters in dual
chambers form tight junctions and exhibit features of polarity, with
expression of megalin exclusively on the upper (apical) surface. After
the addition of unlabeled Tg to the upper chamber and incubation at 37
C, some Tg was transcytosed intact across FRTL-5 cells into the lower
chamber. Two antimegalin ectodomain antibodies precipitated transcytosed
Tg in fluids collected from the lower chamber. After the addition of Tg
to surface-biotinylated FRTL-5 cells, an anti-Tg antibody and the two
antimegalin ectodomain antibodies precipitated high molecular mass
biotinylated material in fluids collected from the lower chamber,
corresponding to much of the megalin ectodomain, as well as smaller
amounts of lower molecular mass material. The results indicate that Tg
transcytosed across FRTL-5 cells remains complexed with megalin
ectodomain components, which we refer to as megalin secretory
components.
In aminotriazole-treated rats, which develop increased megalin-mediated
Tg transcytosis, antimegalin antibodies precipitated some of the Tg in
the serum. Tg was also precipitated by antimegalin antibodies in sera
from patients with Graves’ disease, in which we found increased megalin
expression on the apical surface of thyrocytes. In contrast, in
thyroidectomized patients with metastatic papillary thyroid carcinoma,
in whom Tg is directly secreted by neoplastic thyroid cells into the
circulation rather than transcytosed, serum Tg was not precipitated by
antimegalin antibodies. The detection of Tg-megalin complexes may help
identify the source of serum Tg in patients with thyroid diseases.
Συγγραφείς:
Marino, M
Chiovato, L
Mitsiades, N
Latrofa, F
Andrews, D
and Tseleni-Balafouta, S
Collins, AB
Pinchera, A
McCluskey,
RT
