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Abstract
Lactoferrin (Lf), a major iron-binding protein in human milk, has been suggested to
have multiple biological roles such as facilitating iron absorption, modulating the
immune system, embryonic development, and cell proliferation. Our previous binding
studies suggested the presence of a specific receptor for Lf (LfR) in the small intestine
of newborn infants, which may facilitate iron absorption. We here report the cloning
and the functional expression of the human intestinal LfR and the evidence of its
involvement in iron metabolism. The entire coding region of the LfR cDNA was cloned
by PCR based on amino acid sequences of the purified native LfR (nLfR). The recombinant
LfR (rLfR) was then expressed in a baculovirus-insect cell system and purified by
immobilized human Lf (hLf) affinity chromatography where binding of hLf to the rLfR
was partially Ca(2+) dependent. The apparent molecular mass was 136 kDa under nonreducing
conditions and 34 kDa under reducing conditions. 125I-hLf bound to the rLfR with an
apparent K(d) of approximately 360 nM. These biochemical properties of the rLfR are
similar to those of the nLfR. RT-PCR revealed that the gene was expressed at high
levels in fetal small intestine and in adult heart and at lower levels in Caco-2 cells.
PI-PLC treatment of Caco-2 cells indicated that the LfR is GPI anchored. In Caco-2
cells transfected with the LfR gene, 125I-hLf binding and 59Fe-hLf uptake were increased
by 1.7 and 3.4 times, respectively, compared to those in mock-transfected cells. Our
findings demonstrate the presence of a unique receptor-mediated mechanism for nutrient
uptake by the newborn.