LiZIP3 is a cellular zinc transporter that mediates the tightly regulated import of zinc in Leishmania infantum parasites. Issue 3 (11th March 2015)

• Record Type: Journal Article
• Authors: Carvalho, Sandra; Barreira da Silva, Rosa; Shawki, Ali; Castro, Helena; Lamy, Márcia; Eide, David; Costa, Vítor; Mackenzie, Bryan; Tomás, Ana M.
• Is Part Of: Molecular microbiology. Volume 96:Issue 3(2015)
• Page Start: 581
• Page End: 595
• Publication Date: 2015-03-11
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.12957
• Languages: English
• ISSNs: 0950-382X

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>Cellular zinc homeostasis ensures that the intracellular concentration of this element is kept within limits that enable its participation in critical physiological processes without exerting toxic effects. We report here the identification and characterization of the first mediator of zinc homeostasis in <italic>L</italic><italic>eishmania infantum</italic>, <italic>Li</italic>ZIP3, a member of the ZIP family of divalent metal‐ion transporters. The zinc transporter activity of <italic>Li</italic>ZIP3 was first disclosed by its capacity to rescue the growth of <italic>S</italic><italic>accharomyces cerevisiae</italic> strains deficient in zinc acquisition. Subsequent expression of <italic>Li</italic>ZIP3 in <italic>X</italic><italic>enopus laevis</italic> oocytes was shown to stimulate the uptake of a broad range of metal ions, among which Zn<sup>2+</sup> was the preferred <italic>Li</italic>ZIP3 substrate (<italic>K</italic><sub>0.5</sub> ≈ 0.1 μM). Evidence that <italic>Li</italic>ZIP3 functions as a zinc importer in <italic>L</italic><italic>. infantum</italic> came from the observations that the protein locates to the cell membrane and that its overexpression leads to augmented zinc internalization. Importantly, expression and cell‐surface location of <italic>Li</italic>ZIP3 are lost when parasites face high zinc bioavailability. <italic>Li</italic>ZIP3 decline in response to zinc is regulated at the mRNA level in a process involving (a) short‐lived protein(s). Collectively, our data reveal that <italic>Li</italic>ZIP3 enables <italic>L. infantum</italic> to acquire zinc in a highly regulated manner, hence contributing to zinc homeostasis.</p> </abstract>