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Istituto Nazionale della Nutrizione, 00178 Rome, Italy
We
have identified the Dri 27 cDNA on the basis of its upregulated
expression during rat intestinal development. It encodes a hydrophobic
protein of 430 amino acids that shares significant homology with
members of the mammalian zinc transporter family ZnT. The murine
homologue of Dri 27 (named ZnT4) was recently associated with the mouse
mutation "lethal milk." The primary sequence of Dri 27/ZnT4
displays features characteristic of polytopic membrane
proteins. In this paper, we show that Dri 27/ZnT4 is localized in the
membrane of intracellular vesicles, the majority of which concentrate
in the basal cytoplasmic region of polarized enterocytes. A Dri 27/ZnT4
myc-tagged construct, transiently transfected in intestinal
Caco-2 cells, partially colocalizes with the transferrin receptor and
with the
-subunits of the clathrin adaptor complexes AP-1 and AP-2
in a subpopulation of endosomal vesicles. By subcloning distinct
portions of the protein in frame with
glutathione-S-transferase, we also provide experimental
evidence of their function as zinc-binding and
protein-protein-interaction domains.
small intestine; zinc transport; endosomal trafficking
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