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Zinc transporter ZIP10 forms a heteromer with ZIP6 which regulates embryonic development and cell migration

Taylor, Kathryn M., Muraina, Issa A., Brethour, Dylan, Schmitt-Ulms, Gerold, Nimmanon, Thirayost, Ziliotto, Silvia, Kille, Peter and Hogstrand, Christer 2016. Zinc transporter ZIP10 forms a heteromer with ZIP6 which regulates embryonic development and cell migration. Biochemical Journal 473 (16) , pp. 2531-2544. 10.1042/BCJ20160388

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Abstract

There is growing evidence that zinc and its transporters are involved in cell migration during development and in cancer. In the present study, we show that zinc transporter ZIP10 (SLC39A10) stimulates cell motility and proliferation, both in mammalian cells and in the zebrafish embryo. This is associated with inactivation of GSK-3α and -3ß and downregulation of E-cadherin (CDH1). Morpholino-mediated knock-down of zip10 causes delayed epiboly and deformities of the head, eye, heart and tail. Furthermore, zip10 deficiency results in overexpression of cdh1, zip6 and stat3, the latter gene product driving transcription of both zip6 and zip10. The non-reduntant requirement of Zip6 and Zip10 for epithelial to mesenchymal transition (EMT) is consistent with our finding that they exist as a heteromer. We postulate that a subset of ZIPs carrying PrP-like ectodomains, including ZIP6 and ZIP10, are integral to cellular pathways and plasticity programs, such as EMT.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Biosciences
Subjects: R Medicine > RM Therapeutics. Pharmacology
Publisher: Portland Press
ISSN: 0264-6021
Funders: Wellcome Trust
Date of First Compliant Deposit: 19 July 2016
Date of Acceptance: 2 June 2016
Last Modified: 29 Jan 2020 16:15
URI: http://orca-mwe.cf.ac.uk/id/eprint/92949

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