Abstract (provisional)

Background

Zinc is key to the function of many proteins but the process of dietary zinc absorption is not well clarified. Our current knowledge about dietary zinc absorption is fragmented and mostly from incomplete mammalian studies. To gain a comprehensive picture of this process here we systematically characterized all zinc transporters, i.e., the Zip and ZnT family members, for their possible roles in dietary zinc absorption in a genetic amenable model organism-Drosophila melanogaster.

Results

A set of plasma-membrane-resident zinc transporters is identified responsible for absorbing zinc from the lumen into the enterocyte and subsequent zinc exit to circulation. dZip1 and dZip2, two functionally overlapping zinc importers, are responsible for absorbing zinc from the lumen into the enterocyte. Zinc exit to circulation is mediated through another two functionally overlapping zinc exporters, dZnT1 and its homologue CG5130 (dZnT77C). Somewhat surprisingly, the array of intracellular ZnT proteins including the Golgi-resident dZnT7, appears not directly involved in dietary zinc absorption. By modulating zinc status in different parts of the body, we found that zinc absorption regulation, in contrast to that of iron, is inert to its bodily status or needs. The zinc transporters that are involved in dietary zinc absorption, including importers dZip1, dZip2 and exporter dZnT1, are respectively regulated at the RNA and protein levels by zinc in the enterocyte.

Conclusions

Our study of using Drosophila thus starts to reveal a comprehensive sketch of dietary zinc absorption and its regulation control in a model organism, a process which is still incompletely understood in mammalian organisms. The knowledge gained will act as a reference for future mammalian studies and also enable an appreciation of this important process from an evolutionary perspective.

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