Drosophila ABC transporter, DmHMT-1, confers tolerance to cadmium DmHMT-1 and its yeast homolog, SpHMT-1, are not essential for vacuolar phytochelatin sequestration

Thanwalee Sooksa-nguan, Bakhtiyor Yakubov, Volodymyr I. Kozlovskyy, Caitlin M. Barkume, Kevin J. Howe, Theodore W. Thannhauser, Michael A. Rutzke, Jonathan J. Hart, Leon V. Kochian, Philip A. Rea, Olena K. Vatamaniuk

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

Half-molecule ATP-binding cassette transporters of the HMT-1 (heavy metal tolerance factor 1) subfamily are required for Cd 2+ tolerance in Schizosaccharomyces pombe, Caenorhab-ditis elegans, and Chlamydomonas reinhardtii. Based on studies of S. pombe, it has been proposed that SpHMT-1 transports heavy metal-phytochelatin (PC) complexes into the vacuolyso-somal compartment. PCs are glutathione derivatives synthesized by PC synthases (PCS) in plants, fungi, and C. elegans in response to heavy metals. Our previous studies in C. elegans, however, suggested that HMT-1 and PCS-1 do not necessarily act in concert in metal detoxification. To further explore this inconsistency, we have gone on to test whether DmHMT-1, an HMT-1 from a new source, Drosophila, whose genome lacks PCS homologs, functions in heavy metal detoxification. In so doing, we show that heterologously expressed DmHMT-1 suppresses the Cd 2+ hypersensitivity of S. pombe hmt-1 mutants and localizes to the vacuolar membrane but does not transport Cd·PC complexes. Crucially, similar analyses of S. pombe hmt-1 mutants extend this finding to show that SpHMT-1 itself either does not transport Cd-PC complexes or is not the principal Cd·PC/apoPC transporter. Consistent with this discovery and with our previous suggestion that HMT-1 and PCS-1 do not operate in a simple linear metal detoxification pathway, we demonstrate that, unlike PCS-deficient cells, which are hypersensitive to several heavy metals, SpHMT-1- deficient cells are hypersensitive to Cd 2+, but not to Hg 2+ or As 3+. These findings significantly change our current understanding of the function of HMT-1 proteins and invoke a PC-independent role for these transporters in Cd 2+ detoxification.

Original languageEnglish (US)
Pages (from-to)354-362
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number1
DOIs
StatePublished - Jan 2 2009

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