GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

TableEdit

Jump to: navigation, search

PMID:19924247

You don't have sufficient rights on this wiki to edit tables. Perhaps you need to log in. Changes you make in the Table editor will not be saved back to the wiki

See Help for Help on this wiki. See the documentation for how to use the table editor

Citation

Au, C, Benedetto, A, Anderson, J, Labrousse, A, Erikson, K, Ewbank, JJ and Aschner, M (2009) SMF-1, SMF-2 and SMF-3 DMT1 orthologues regulate and are regulated differentially by manganese levels in C. elegans. PLoS ONE 4:e7792

Abstract

Manganese (Mn) is an essential metal that can exert toxic effects at high concentrations, eventually leading to Parkinsonism. A major transporter of Mn in mammals is the divalent-metal transporter (DMT1). We characterize here DMT1-like proteins in the nematode C. elegans, which regulate and are regulated by Mn and iron (Fe) content. We identified three new DMT1-like genes in C. elegans: smf-1, smf-2 and smf-3. All three can functionally substitute for loss of their yeast orthologues in S. cerevisiae. In the worm, deletion of smf-1 or smf-3 led to an increased Mn tolerance, while loss of smf-2 led to increased Mn sensitivity. smf mRNA levels measured by QRT-PCR were up-regulated upon low Mn and down-regulated upon high Mn exposures. Translational GFP-fusions revealed that SMF-1 and SMF-3 strongly localize to partially overlapping apical regions of the gut epithelium, suggesting a differential role for SMF-1 and SMF-3 in Mn nutritional intake. Conversely, SMF-2 was detected in the marginal pharyngeal epithelium, possibly involved in metal-sensing. Analysis of metal content upon Mn exposure in smf mutants revealed that SMF-3 is required for normal Mn uptake, while smf-1 was dispensable. Higher smf-2 mRNA levels correlated with higher Fe content, supporting a role for SMF-2 in Fe uptake. In smf-1 and smf-3 but not in smf-2 mutants, increased Mn exposure led to decreased Fe levels, suggesting that both metals compete for transport by SMF-2. Finally, SMF-3 was post-translationally and reversibly down-regulated following Mn-exposure. In sum, we unraveled a complex interplay of transcriptional and post-translational regulations of 3 DMT1-like transporters in two adjacent tissues, which regulate metal-content in C. elegans.

Links

PubMed PMC2773845 Online version:10.1371/journal.pone.0007792

Keywords

Amino Acid Sequence; Animals; Animals, Genetically Modified; Biological Transport; Caenorhabditis elegans; Caenorhabditis elegans Proteins/metabolism; Cation Transport Proteins/genetics; Cation Transport Proteins/metabolism; Cloning, Molecular; Gene Deletion; Gene Expression Regulation; Iron/chemistry; Manganese/chemistry; Manganese/metabolism; Metals/chemistry; Molecular Sequence Data; Saccharomyces cerevisiae/metabolism; Sequence Homology, Amino Acid

public



Cancel