title: 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.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Guiran
authors.initials: G
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Qiangwang
authors.initials: Q
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Xiaona
authors.initials: X
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing, China zhoubing@mail.tsinghua.edu.cn.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhou
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D004535:Ehlers-Danlos Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005293:Ferritins / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D017136:Ion Transport; D007501:Iron / Q000378:metabolism; D007504:Iron Radioisotopes; D008969:Molecular Sequence Data; D009154:Mutation; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D055571:Secretory Pathway / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D019076:Transgenes
chemical_list: D027682:Cation Transport Proteins; D029721:Drosophila Proteins; D007504:Iron Radioisotopes; D020033:Protein Isoforms; D034741:RNA, Small Interfering; C521172:SLC39A13 protein, human; D003094:Collagen; D005293:Ferritins; D007501:Iron
keywords: Drosophila; Ehlers–Danlos syndrome; Slc39a13; iron transporter; secretory compartments