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J. Biol. Chem., Vol. 277, Issue 2, 879-882, January 11, 2002
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,
From the Department of Molecular Biology and Pharmacology,
Washington University School of Medicine, St.
Louis, Missouri 63110
One of the fundamental differences
among mammals is the mechanism of maintaining the corpus luteum of
pregnancy. Placentation in primates is associated with the production
of the glycoprotein hormone chorionic gonadotropin (CG), which is
secreted into the maternal serum and stimulates progesterone synthesis
from the corpus luteum, which is essential for early development of the embryo. CG together with the pituitary hormones lutropin (LH), follitropin, and thyrotropin constitute the family of glycoprotein hormones comprised of a common
subunit and a hormone-specific
subunit. The LH
and CG
subunits share 85% amino acid sequence identity, and functionally LH and CG are interchangeable. CG
evolved
by a recent gene duplication event from the LH
locus, and despite
the close relationship between them, their modes of secretion are quite
different. CG release from the placenta is apically directed, whereas
LH is released from the basal side of the cell, and the determinant(s)
for this redirected trafficking are unknown. Here, using the polarized
Madin-Darby canine kidney (MDCK) cell line, we provide evidence for the
molecular basis of the different secretory patterns of LH and CG
in vivo. The apical targeting of CG is programmed by a
carboxyl-terminal sequence, which encodes a novel sorting signal. It is
also apparent that the presence of the O-linked
oligosaccharides in the CTP sequence contributes to this apical
routing. The CTP, which is absent in LH, redirects CG to the maternal
serum and permits the unique arrangement for primate placentation. Our
data also show that the MDCK cells can distinguish the different
secretory pathways for the gonadotropins and will be a valuable model
for elucidating the determinants associated with the unique sorting of
these functionally related hormones.
Recipient of an National Research Service Award award from the
National Institutes of Health.
§
To whom correspondence should be addressed: Dept. of Molecular
Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63110. Tel.: 314-362-2556; Fax: 314-361-3560; E-mail: iboime@pcg.wustl.edu.
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