Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
Divalent metal transporter-related protein restricts animals to marine habitats.
Sassa M
,
Takagi T
,
Kinjo A
,
Yoshioka Y
,
Zayasu Y
,
Shinzato C
,
Kanda S
,
Murakami-Sugihara N
,
Shirai K
,
Inoue K
.
???displayArticle.abstract???
Utilization and regulation of metals from seawater by marine organisms are important physiological processes. To better understand metal regulation, we searched the crown-of-thorns starfish genome for the divalent metal transporter (DMT) gene, a membrane protein responsible for uptake of divalent cations. We found two DMT-like sequences. One is an ortholog of vertebrate DMT, but the other is an unknown protein, which we named DMT-related protein (DMTRP). Functional analysis using a yeast expression system demonstrated that DMT transports various metals, like known DMTs, but DMTRP does not. In contrast, DMTRP reduced the intracellular concentration of some metals, especially zinc, suggesting its involvement in negative regulation of metal uptake. Phylogenetic distribution of the DMTRP gene in various metazoans, including sponges, protostomes, and deuterostomes, indicates that it originated early in metazoan evolution. However, the DMTRP gene is only retained in marine species, and its loss seems to have occurred independently in ecdysozoan and vertebrate lineages from which major freshwater and land animals appeared. DMTRP may be an evolutionary and ecological limitation, restricting organisms that possess it to marine habitats, whereas its loss may have allowed other organisms to invade freshwater and terrestrial habitats.
Fig. 1. Comparison of amino acid sequences of the crown-of-thorns starfish (COTS), Acanthaster planci, divalent metal transporter (ApDMT) and DMT-related protein (ApDMTRP).Alignment was carried out with MAFFT version 7. Identical amino acids are indicated by asterisks. Conservative and semi-conservative substitutions are indicated with colons and periods, respectively. Black arrows indicate consensus transport motifs (CTMs). Blue arrowheads indicate positions of introns. Black boxes indicate functionally important amino acid residues.
Fig. 2. Conserved motif locations of the crown-of-thorns starfish (COTS), Acanthaster planci, divalent metal transporter (ApDMT) and DMT-related protein (ApDMTRP).Conserved domains were identified using the MEME web server. Colored boxes indicate motifs. Black lines indicate whole proteins and numbers on the right side indicate the length of the encoded amino acid sequence of each gene.
Fig. 3. Genes around divalent metal transporter (DMT) and DMT-related protein (DMTRP) genes.a The crown-of-thorns starfish (COTS), Acanthaster planci and b the European starfish, Asterias rubens. Scaffold names and chromosome numbers are indicated on the left. Genes and their orientations are indicated by pentagons of the same size. DMT, DMTRP, and other genes are indicated in blue, magenta, and gray. Numbers above the COTS scaffold indicate start or end positions of gene locations. Protein names and gene IDs are listed in Table S2.
Fig. 4. Maximum-likelihood trees of divalent metal transporter (DMT)-like protein sequences obtained from databases.A tree constructed using metazoan sequences. The tree was rooted using the sequence of a choanoflagellate, Monosiga brevicollis, as an outgroup. Bootstrap values more than 70% are indicated at nodes. The scale bar represents a phylogenetic distance of 0.2 substitutions per site.
Fig. 5. Subcellular localization of the crown-of-thorns starfish (COTS), Acanthaster planci, divalent metal transporter (ApDMT) and DMT-related proteins (ApDMTRP) fused with EGFP expressed in yeasts.Yeasts (DY1457) were transformed with ApDMT and ApDMTRP genes fused to the EGFP gene and observed with fluorescent and phase contrast microscopy. Yeasts expressing EGFP alone (EGFP) and those transformed with an empty vector (EV) are shown for comparison. The scale bar is 10 μm.
Fig. 6. Heavy metal accumulation in yeasts in which the crown-of-thorns starfish (COTS), Acanthaster planci, divalent metal transporter (ApDMT) and DMT-related proteins (ApDMTRP) were expressed.Wild-type or metal uptake-deficient strains of yeasts were transformed with the expression vector pDR195 containing ApDMT or ApDMTRP or empty vector (EV), and exposed to media containing FeCl3 (a, b), MnSO4 (c, d), ZnCl2 (e, f), CdCl2 (g), PbCl2 (h), or CuCl2 (i). The vertical axis shows the intracellular concentration measured by ICP-MS normalized by yeast optical density (OD600). The horizontal axis shows the names of expressed genes/yeast strains. Each bar represents the mean ± SEM (n = 3). One or two asterisks on the bar represent statistical significance by one way ANOVA with Tukey’s post-hoc HSD test at p < 0.01(**) or p < 0.05(*). DY, wild-type strain of DEY1453 and ZHY3; DEY, Fe-uptake-deficient yeast strain DEY1453; ZHY, Zn-uptake-deficient yeast strain ZHY3; BY4743, wild-type strain of single mutant strain HomDip-YOL122C lacking SMF1; smf1, Mn-uptake-deficient yeast strain HomDip-YOL122C lacking SMF1. Dot plots shows individual data points. Dot plots data are in Supplementary Data 2.
Bailey,
Fitting a mixture model by expectation maximization to discover motifs in biopolymers.
1994, Pubmed
Bailey,
Fitting a mixture model by expectation maximization to discover motifs in biopolymers.
1994,
Pubmed
Blackwell,
Understanding the multiple functions of Nramp1.
2000,
Pubmed
Bozzi,
Crystal Structure and Conformational Change Mechanism of a Bacterial Nramp-Family Divalent Metal Transporter.
2016,
Pubmed
Bozzi,
Structures in multiple conformations reveal distinct transition metal and proton pathways in an Nramp transporter.
2019,
Pubmed
Bozzi,
Conserved methionine dictates substrate preference in Nramp-family divalent metal transporters.
2016,
Pubmed
Capella-Gutiérrez,
trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses.
2009,
Pubmed
Cellier,
Nramp defines a family of membrane proteins.
1995,
Pubmed
Dix,
The FET4 gene encodes the low affinity Fe(II) transport protein of Saccharomyces cerevisiae.
1994,
Pubmed
Ehrnstorfer,
Crystal structure of a SLC11 (NRAMP) transporter reveals the basis for transition-metal ion transport.
2014,
Pubmed
Formigari,
Zinc, antioxidant systems and metallothionein in metal mediated-apoptosis: biochemical and cytochemical aspects.
2007,
Pubmed
Glover,
The good, the bad and the slimy: experimental studies of hagfish digestive and nutritional physiology.
2019,
Pubmed
Gruenheid,
Identification and characterization of a second mouse Nramp gene.
1995,
Pubmed
Gunshin,
Cloning and characterization of a mammalian proton-coupled metal-ion transporter.
1997,
Pubmed
Hall,
The crown-of-thorns starfish genome as a guide for biocontrol of this coral reef pest.
2017,
Pubmed
,
Echinobase
Inoue,
Genomics and Transcriptomics of the green mussel explain the durability of its byssus.
2021,
Pubmed
Katoh,
MAFFT multiple sequence alignment software version 7: improvements in performance and usability.
2013,
Pubmed
Katoh,
MAFFT online service: multiple sequence alignment, interactive sequence choice and visualization.
2019,
Pubmed
Kimura,
The Functions of Metallothionein and ZIP and ZnT Transporters: An Overview and Perspective.
2016,
Pubmed
King,
The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans.
2008,
Pubmed
Käll,
A combined transmembrane topology and signal peptide prediction method.
2004,
Pubmed
Marciani,
Modulation of DMT1 activity by redox compounds.
2004,
Pubmed
Migliaccio,
Maternal Exposure to Cadmium and Manganese Impairs Reproduction and Progeny Fitness in the Sea Urchin Paracentrotus lividus.
2015,
Pubmed
,
Echinobase
Migliaccio,
Stress response to cadmium and manganese in Paracentrotus lividus developing embryos is mediated by nitric oxide.
2014,
Pubmed
,
Echinobase
Neves,
Natural history of SLC11 genes in vertebrates: tales from the fish world.
2011,
Pubmed
Nevo,
The NRAMP family of metal-ion transporters.
2006,
Pubmed
Nishimura,
An auxin-based degron system for the rapid depletion of proteins in nonplant cells.
2009,
Pubmed
Ochiai,
Copper and the biological evolution.
1983,
Pubmed
Okubo,
Cadmium transport by human Nramp 2 expressed in Xenopus laevis oocytes.
2003,
Pubmed
Qin,
Genome-Wide Identification and Expression Analysis of NRAMP Family Genes in Soybean (Glycine Max L.).
2017,
Pubmed
Richer,
Horizontal gene transfer of "prototype" Nramp in bacteria.
2003,
Pubmed
Sacher,
Properties of the mammalian and yeast metal-ion transporters DCT1 and Smf1p expressed in Xenopus laevis oocytes.
2001,
Pubmed
Stamatakis,
RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models.
2006,
Pubmed
Tandy,
Nramp2 expression is associated with pH-dependent iron uptake across the apical membrane of human intestinal Caco-2 cells.
2000,
Pubmed
Toyohara,
Scallop DMT functions as a Ca2+ transporter.
2005,
Pubmed
Ullah,
Evolution, and functional analysis of Natural Resistance-Associated Macrophage Proteins (NRAMPs) from Theobroma cacao and their role in cadmium accumulation.
2018,
Pubmed
Vidal,
Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg.
1993,
Pubmed
West,
Two related genes encoding extremely hydrophobic proteins suppress a lethal mutation in the yeast mitochondrial processing enhancing protein.
1992,
Pubmed
Xu,
Structure and metal exchange in the cadmium carbonic anhydrase of marine diatoms.
2008,
Pubmed
Yılmaz,
Review of heavy metal accumulation on aquatic environment in Northern East Mediterrenean Sea part I: some essential metals.
2017,
Pubmed
Zhao,
The ZRT2 gene encodes the low affinity zinc transporter in Saccharomyces cerevisiae.
1996,
Pubmed
Ziller,
Metallothionein diversity and distribution in the tree of life: a multifunctional protein.
2018,
Pubmed
