The metal transporter ZIP13 supplies iron into the secretory pathway in Drosophila melanogaster

Abstract

The intracellular iron transfer process is not well understood, and the identity of the iron transporter responsible for iron delivery to the secretory compartments remains elusive. In this study, we show Drosophila ZIP13 (Slc39a13), a presumed zinc importer, fulfills the iron effluxing role. Interfering with dZIP13 expression causes iron-rescuable iron absorption defect, simultaneous iron increase in the cytosol and decrease in the secretory compartments, failure of ferritin iron loading, and abnormal collagen secretion. dZIP13 expression in E. coli confers upon the host iron-dependent growth and iron resistance. Importantly, time-coursed transport assays using an iron isotope indicated a potent iron exporting activity of dZIP13. The identification of dZIP13 as an iron transporter suggests that the spondylocheiro dysplastic form of Ehlers–Danlos syndrome, in which hZIP13 is defective, is likely due to a failure of iron delivery to the secretory compartments. Our results also broaden our knowledge of the scope of defects from iron dyshomeostasis.DOI: http://dx.doi.org/10.7554/eLife.03191.001

The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism

“…The mutant also exhibits defects in membrane protein trafficking and elevated ER stress (129). In contrast to mammalian ZIP13, dZip13 is identified as an iron exporter to supply iron into the secretory pathway (450). Phenotypes of knockdowns or overexpression of Drosophila ZnT and ZIP transporters, and genetic interactions between them have been extensively investigated and summarized (257,258).…”

The trafficking of metal ion transporters of the Zrt‐ and Irt‐like protein family

“…The mutations identified lead to instability of the protein (via rapid proteasomal degradation) . Studies of the D. melanogaster orthologue of ZIP13 (dZIP13) suggest that dZIP13 may transport essential iron into (rather than out of) ER and Golgi compartments, in order to provide iron for iron‐requiring enzymes . The mechanisms for trafficking ZIP13 to ER and Golgi are presently unknown.…”

Biogenesis of zinc storage granules inDrosophila melanogaster

“…In Drosophila, iron availability is linked to key developmental signals, such as ecdysone synthesis (Llorens et al, 2015;Palandri et al, 2015), and to processes such as the formation of epithelial septate junctions (Tiklová et al, 2010), the functionality of the circadian clock (Mandilaras and Missirlis, 2012), and the induction of mitotic events (Li, 2010). So far, a single iron transporter moving iron into the cytosol has been identified in flies (Orgad et al, 1998;Bettedi et al, 2011) and a single iron exporter has been suggested to traffic iron from the cytosol into the endoplasmic reticulum and Golgi apparatus (Xiao et al, 2014), where insect ferritin resides (Missirlis et al, 2007;Rosas-Arellano et al, 2016).…”