Abstract:Background: ZIP13 protein is important for connective tissue development, which has not been characterized in detail. Results: ZIP13 is an eight-transmembrane protein with a unique hydrophilic region that forms a homo-dimer. Conclusion: ZIP13 is a homo-dimerized zinc transporter that possesses domains that are not found in other LZT families. Significance: The data and materials provide useful information and opportunity for further structural and functional analyses of ZIP13.
“…S4D, E). A role for ZIP13 in myogenesis might be hypothezised, as lack of functional ZIP13 is related to Ehlers-Danlos syndrome, which is characterized by skeletal and connective tissue abnormalities [49,51,105]. Both ZnT5 gene and protein showed a non-significant but observable 2-fold increase in expression after 72 h of differentiation (Supp.…”
Section: Resultsmentioning
confidence: 99%
“…ZIP9 is located at the cell surface and TGN [47,48] and is considered to be an androgen receptor in addition to its role in Zn transport [48]. ZIP13 mobilizes Zn to the TGN and secretory vesicles, controls Zn homeostasis in the ER and is involved in BMP/TGF-β/Smad signaling pathway [49–51]. …”
Zinc transporters facilitate metal mobilization and compartmentalization, playing a key role in cellular development. Little is known about the mechanisms and pathways of Zn movement between Zn transporters and metalloproteins during myoblast differentiation. We analyzed the differential expression of ZIP and ZnT transporters during C2C12 myoblast differentiation. Zn transporters account for a transient decrease of intracellular Zn upon myogenesis induction followed by a gradual increase of Zn in myotubes. Considering the subcellular localization and function of each of the Zn transporters, our findings indicate that a fine regulation is necessary to maintain correct metal concentrations in the cytosol and subcellular compartments to avoid toxicity, maintain homeostasis, and for loading metalloproteins needed during myogenesis. This study advances our basic understanding of the complex Zn transport network during muscle differentiation.
“…S4D, E). A role for ZIP13 in myogenesis might be hypothezised, as lack of functional ZIP13 is related to Ehlers-Danlos syndrome, which is characterized by skeletal and connective tissue abnormalities [49,51,105]. Both ZnT5 gene and protein showed a non-significant but observable 2-fold increase in expression after 72 h of differentiation (Supp.…”
Section: Resultsmentioning
confidence: 99%
“…ZIP9 is located at the cell surface and TGN [47,48] and is considered to be an androgen receptor in addition to its role in Zn transport [48]. ZIP13 mobilizes Zn to the TGN and secretory vesicles, controls Zn homeostasis in the ER and is involved in BMP/TGF-β/Smad signaling pathway [49–51]. …”
Zinc transporters facilitate metal mobilization and compartmentalization, playing a key role in cellular development. Little is known about the mechanisms and pathways of Zn movement between Zn transporters and metalloproteins during myoblast differentiation. We analyzed the differential expression of ZIP and ZnT transporters during C2C12 myoblast differentiation. Zn transporters account for a transient decrease of intracellular Zn upon myogenesis induction followed by a gradual increase of Zn in myotubes. Considering the subcellular localization and function of each of the Zn transporters, our findings indicate that a fine regulation is necessary to maintain correct metal concentrations in the cytosol and subcellular compartments to avoid toxicity, maintain homeostasis, and for loading metalloproteins needed during myogenesis. This study advances our basic understanding of the complex Zn transport network during muscle differentiation.
“…Notably for dZIP13 and hZIP13, there is only a single His residue in a generally histidine-rich region (2–14 His) between TM3 and TM4. The highly conserved potential metalloprotease His-Glu- X - X -His (HE XX H, where X is any amino acid) motif, located within TM5 (Bin et al, 2011) of LZT proteins, is also found in dZIP13 (Figure 1A). 10.7554/eLife.03191.003Figure 1.Sequence analysis of Drosophila ZIP13.( A ) Alignment of Drosophila ZIP13 (dZIP13, the top), human ZIP13 (hZIP13, the middle), and human ZIP4 (hZIP4, the bottom) proteins.…”
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
“…This evidence indicates that ZIP13 is involved in connective tissue development. Moreover, it has been revealed that the loss of function of ZIP13 causes the spondylocheiro dysplastic form of Ehlers-Danlos syndrome (OMIM 612350), a hereditary connective tissue disorder [121][122][123].…”
Section: Zinc Transporters and Skin Disordersmentioning
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