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The nuclear Zn transporter ZIP11 is necessary for the proliferation of HeLa cells
Author(s) -
Kan Julia,
Syed Sabriya,
Carlson Alyssa,
PadillaBenavides Teresita
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.00445
Subject(s) - cytosol , transporter , organelle , microbiology and biotechnology , internalization , nucleus , chemistry , biochemistry , transport protein , nuclear transport , divalent , biology , cell nucleus , cell , gene , enzyme , organic chemistry
Zinc (Zn) is the second most abundant and essential trace element for all organisms. Under physiological conditions, Zn exists as a non‐redox active divalent cation (Zn 2+ ). Zn is part of several biological processes, including transcriptional regulation, signaling, catalysis, and as a structural component of proteins. A complex subcellular network of Zn transporters is indispensable to ensure the adequate distribution of Zn and to maintain homeostasis. Among these, the family of importers Zrt/Irt‐like protein (ZIP) constitutes 14 members (ZIP1‐ZIP14) that mobilize Zn into the cytosol. Some ZIP proteins can also transport iron, manganese, and cadmium. Research has shown that the expression of these transporters varies among tissues and during the different developmental stages. The presence of ZIP transporters at various cellular locations is essential for defining the net cellular transport of Zn. In cells, about 50% of Zn is cytosolic, 30‐40% localizes in the nucleus, and 10% in the membrane. Normally, the ion is bound to proteins or sequestered in organelles and vesicles. Extensive research has focused on Zn internalization in mammalian cells. However, little attention has been given to the mobilization of the ion within the cells and the organelles, including the nucleus. In this regard, ZIP11 is the only ZIP transporter localized in the nucleus of mammalian cells. Sequence analyses indicated that Zip11 expression is responsive to Zn. However, the cellular role and the mechanism and direction of transport of ZIP11 are not defined yet. Therefore, we hypothesized that ZIP11 is a nuclear Zn transporter essential to maintaining nuclear Zn homeostasis in mammalian cells. To test this idea, our laboratory is using a well‐established model of shRNA to knock‐down Zip11 in normal fibroblasts and the cancer cell line HeLa. Preliminary data shows that partial deletion of Zip11 significantly reduced the proliferation rate of HeLa cells, and when HeLa cells reached confluency, they acquired an epithelial morphology. Experiments to determine the expression of epithelial vs . cancer markers are in progress. We will also investigate the direction of transport of ZIP11 by measuring changes in nuclear and cytosolic Zn levels between wild type cells and cells with decreased expression of the transporter. Our work has the potential to discover a novel molecular mechanism where nuclear Zn homeostasis is an essential factor for cancer progression.