Ks. Graebert et al., LOCALIZATION AND REGULATED RELEASE OF ALZHEIMER AMYLOID PRECURSOR-LIKE PROTEIN IN THYROCYTES, Laboratory investigation, 72(5), 1995, pp. 513-523
BACKGROUND: Dysregulation in the processing of the Alzheimer precursor
protein (APP) is thought to be central to the deposition of the beta-
A4 peptide and to the pathogenesis of Alzheimer's disease. Expression
and release of APP has also been known to mediate cell-matrix interact
ions and to participate in the regulation of cell proliferation. It ha
s also been shown that APP is a member of a family of closely related
proteins. This family comprises different splice-forms of APP and APP-
like proteins (APP/APLP). Because of the specific processing of export
able proteins, thyrocytes represent a particularly useful cell type fo
r the study of the processing of APP/APLP (especially proteolysis and
iodination) as an indication of cell surface expression and for the st
udy of the regulation of these functions. EXPERIMENTAL DESIGN: Rats we
re treated in vivo with propylthiouracil, which is known to cause a ri
se of serum thyroid-stimulating hormone (TSH) levels and maximum stimu
lation of thyroid function and growth. The expression of APP/APLP was
analyzed in rat thyroid tissue and in a continuous cell line (FRTL-5)
by immunofluorescence staining and by sodium dodecyl sulfate polyacryl
amide gel electrophoresis and immunoblotting. Using FRTL-5 cells, secr
etion and turnover were analyzed by biosynthetic radiolabeling and imm
unoprecipitation of APP/APLP. RESULTS: APP/APLP was detected in follic
le cells and in the follicle lumen of resting thyroid glands. In propy
lthiouracil-treated rats, the complete endocytic removal of the lumina
l content coincided with the pronounced visualization of APP/APLP in t
he extrafollicular space, where it was associated with proliferating e
ndothelial cells and fibroblasts. In FRTL-5 cells, APP/APLP was locali
zed mainly in the Golgi complex and in compartments along the endocyti
c pathway, including lysosomes, where degradation of APP/APLP occurred
. Mature and immature forms of APP/APLP became iodinated upon reaching
the plasma membrane. Part of the extracellular portion of APP/APLP wa
s released by these cells cleavage and secretion mechanisms. CONCLUSIO
NS: The observations show the expression, maturation, and secretion of
APP/APLP in thyrocytes and the up-regulation of these processes by TS
H. Part of the immature APP/APLP appeared on the cell surface as indic
ated by its iodination. Apparently, this portion of immature APP/APLP
escaped maturation during its transport to the cell surface.