Studies On The Mechanism For Dietary Zinc Absorption In Drosophila Melanogaster

Zinc is an essential micronutrient which serves as a structural, catalytical, orregulatory component of many zinc-containing proteins. It is important in almost allaspects of biology. Both low zinc and too much zinc accumulation are harmful for cellsand organisms to survive, which therefore evolved multiple pathways to maintain thezinc homeostasis. One of the most important pathways of maintaining zinc homeostasisis dietary zinc absorption. Zip4mutation leads to the human genetic disease,Acrodermatitis Enteropathica. Mammalian Zip4has been suspected to localize on theapical membrane of the enterocyte and absorb dietary zinc into the cytosol of the gutcells, while ZnT1has been clarified to pump zinc from gut cells into the circulation inDrosophila and mammalian systems. But whether the other zinc transporters, such asthose localized on the plasma membrane or the secretion pathway, are involved indietary zinc absorption is still unknown. Briefly, there has been no systemic study on allzinc transporters in dietary zinc absorption in a multicellular organism, which should bewell studied.To gain a more complete picture of zinc absorptive process, here we systematicallycharacterize other candidate zinc importers and exporters, i.e., the Zip and ZnT familymembers, for their possible roles in Drosophila dietary zinc absorption. Knocking downdZip1or dZip2specifically in Drosophila midgut leads to reduced zinc level in the body,and the double RNAi can severe the sensitivity to dietary zinc deficiency. Both of thetwo proteins are located on the apical membrane of the enterocyte and have zinctransport activity into the cells. These results demonstrate dZip1and dZip2functioncorporately in zinc absorption from the lumen into the enterocyte. At the basalmembrane, CG5130is distributed at the plasma membrane and has zinc release activityin cultural cells. Its gut-specific knockdown causes reduced zinc status in the body andseveres the sensitivity of dZnT1RNA interference to dietary zinc deficiency. Theseexperiments suggest the absorbed zinc is exported through CG5130and ZnT1intocirculation. However, gut-specific knockdown of a set of intracellular ZnT proteinsincluding the Golgi-resident dZnT7, results no dietary zinc absorption defect, and this isso even in a sensitized background with dZnT1knocked-down, suggesting intracellular trafficking pathway is not directly involved in the exit of the absorbed zinc for systemicuse. When dietary zinc level was changed, we found dZip1and dZip2can be regulatedat the RNA level and dZnT1at the post-transcriptional level. By modulating zinc statusin different parts of the body, we found that zinc absorption regulation is inert to thebodily zinc level. Our study of using Drosophila thus starts to reveal a comprehensivesketch of dietary zinc absorption and its control in a model organism.