Abstract:
ZIP4 and ZIP5 belong to the Zrt-Irt-like proteins (SLC39A) family of metal ion transporters. Mutations in hZIP4 cause
acrodermatitis enteropathica, which reflects an inability to absorb adequate zinc. ZIP5 is a close paralog to ZIP4. To further understand the mechanism of regulation for ZIP4 and ZIP5, we analyzed proximal intestine and pancreas from weanling mice fed a zinc deficient (ZnD) or zinc adequate (ZnA) diet for 10 days followed by zinc gavage (or saline control). Also, pregnant dams were fed ZnD diet beginning on d8 of pregnancy with tissues collected on d14. Intestinal and visceral-yolk-sac (VYS) MT-I mRNA was upregulated after zinc gavage. Intestinal and VYS ZIP4 mRNA was induced during ZnD but unchanged after zinc gavage and ZIP5 and ZIP1 mRNAs were unaltered by zinc. In mice fed a ZnA diet, ZIP4 protein was rare and undetected on the apical membrane of enterocytes or VYS and ZIP5 protein was detected on basolateral membranes of those cells and pancreatic acinar cells. During ZnD, ZIP4 protein accumulated at the apical membrane of enterocytes and VYS while ZIP5 was removed from the basolateral membranes and degraded in those tissues as well as acinar cells. Within 4h of zinc repletion, ZIP4 protein was internalized and rapidly degraded in enterocytes whereas ZIP5 protein re-accumulated on the basolateral membranes of enterocytes and acinar cells. By 6h after zinc gavage in VYS, ZIP4 was internalized but not degraded and ZIP5 was rapidly synthesized. Our studies suggest that ZIP4 and ZIP5 are predominately regulated by posttranscriptional mechanisms.
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