Jump to main content
Jump to site search

Issue 3, 2017
Previous Article Next Article

Zinc transport and the inhibition of the L-type calcium channel are two separable functions of ZnT-1

Author affiliations

Abstract

Traditionally, proteins are considered to perform a single role, be it as an enzyme, a channel, a transporter or as a structural scaffold. However, recent studies have described moonlighting proteins that perform distinct and independent functions; for example, TRPM7 is both an ion channel and a kinase. ZnT-1 is a member of the Carrier Diffusion Facilitator family that is expressed throughout the phylogenetic tree from bacteria to humans. Since its cloning in 1995, ZnT-1 is considered a major extruder of Zn2+ based on its capability to protect cells against zinc toxicity. Recently, we reported that ZnT-1 inhibits the L-type calcium channel (LTCC), a major Zn2+ and Ca2+ entry pathway. Here we show that ZnT-1 is a dual-function protein by demonstrating that its abilities to exchange Zn2+/H+ and to inhibit the LTCC are independent of each other and are mediated by different parts of the protein. Specifically, mutations in the membrane-spanning helices that render ZnT-1 unable to transport zinc do not prevent it from inhibiting the LTCC. Moreover, a fragment consisting of the intracellular ZnT-1 C-terminal, which lacks all ion-transfer segments, inhibits the LTCC as efficiently as wild-type ZnT-1. Our data therefore indicates that ZnT-1 performs two structurally independent functions related to zinc homeostasis.

Graphical abstract: Zinc transport and the inhibition of the L-type calcium channel are two separable functions of ZnT-1

Back to tab navigation
Please wait while Download options loads

Publication details

The article was received on 15 Dec 2016, accepted on 04 Jan 2017, published on 04 Jan 2017 and first published online on 04 Jan 2017


Article type: Paper
DOI: 10.1039/C6MT00296J
Citation: Metallomics, 2017,9, 228-238
  •   Request permissions

    Zinc transport and the inhibition of the L-type calcium channel are two separable functions of ZnT-1

    E. Shusterman, O. Beharier, S. Levy, R. Zarivach, Y. Etzion, C. R. Campbell, I. Lee, A. Dinudom, D. I. Cook, A. Peretz, A. Katz, D. Gitler and A. Moran, Metallomics, 2017, 9, 228
    DOI: 10.1039/C6MT00296J

Search articles by author