A Multi-domain Snail Metallothionein Increases Cadmium Resistance and Fitness in Caenorhabditis Elegans

Overview

Journal Sci Rep

Specialty Science

Date 2024 Oct 27

PMID 39462019

Authors

Andreas Andric

Michael Niederwanger

Eva Albertini

Pidder Jansen-Durr

Stephen R Sturzenbaum

Reinhard Dallinger

Veronika Pedrini-Martha

Alexander K H Weiss

Affiliations

Soon will be listed here.

Abstract

Metallothioneins (MTs) are a family of mostly low-molecular weight, cysteine-rich proteins capable of specific metal-ion binding that are involved in metal detoxification and homeostasis, as well as in stress response. In contrast to most other animal species which possess two-domain (bidominial) MTs, some gastropod species have evolved Cd-selective multidomain MTs (md-MTs) consisting of several concatenated β3 domains and a single C-terminal β1 domain. Each domain contains three-metal ion clusters and binds three metal ions. The terrestrial snail Alinda biplicata possesses, among other MT isoforms, an md-MT with nine β3 domains and a C-terminal β1 domain (termed 10md-MT), capable of binding up to 30 Cd ions per protein molecule. In the present study, the Alinda biplicata 10md-MT gene and a truncated version consisting of one β3 domain and a single C-terminal β1 domain (2d-MT) were introduced into a Caenorhabditis elegans knock-out strain lacking a native MT gene (mtl-1). The two snail MT constructs consistently increased Cd resistance, and partially improved morphological, life history and physiological fitness traits in the nematode model host Caenorhabditis elegans. This highlights how the engineering of transgenic Caenorhabditis elegans strains expressing snail MTs provides an enhancement of the innate metal detoxification mechanism and in doing so provides a platform for enhanced mechanistic toxicology.

References

Min K, Terano Y, Onosaka S, Tanaka K . Induction of hepatic metallothionein by nonmetallic compounds associated with acute-phase response in inflammation. Toxicol Appl Pharmacol. 1991; 111(1):152-62. DOI: 10.1016/0041-008x(91)90144-4. View

Gunther V, Lindert U, Schaffner W . The taste of heavy metals: gene regulation by MTF-1. Biochim Biophys Acta. 2012; 1823(9):1416-25. DOI: 10.1016/j.bbamcr.2012.01.005. View

Qu W, Pi J, Waalkes M . Metallothionein blocks oxidative DNA damage in vitro. Arch Toxicol. 2012; 87(2):311-21. PMC: 3554841. DOI: 10.1007/s00204-012-0927-y. View

Murphy B, Andrews G, Bittel D, Discher D, McCue J, Green C . Activation of metallothionein gene expression by hypoxia involves metal response elements and metal transcription factor-1. Cancer Res. 1999; 59(6):1315-22. View

Choong G, Liu Y, Templeton D . Interplay of calcium and cadmium in mediating cadmium toxicity. Chem Biol Interact. 2014; 211:54-65. DOI: 10.1016/j.cbi.2014.01.007. View

Koizumi S, Suzuki K, Ogra Y, Yamada H, Otsuka F . Transcriptional activity and regulatory protein binding of metal-responsive elements of the human metallothionein-IIA gene. Eur J Biochem. 1999; 259(3):635-42. DOI: 10.1046/j.1432-1327.1999.00069.x. View

Swain S, Wren J, Sturzenbaum S, Kille P, Morgan A, Jager T . Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans. BMC Syst Biol. 2010; 4:32. PMC: 2857823. DOI: 10.1186/1752-0509-4-32. View

Schmielau L, Dvorak M, Niederwanger M, Dobieszewski N, Pedrini-Martha V, Ladurner P . Differential response to Cadmium exposure by expression of a two and a three-domain metallothionein isoform in the land winkle Pomatias elegans: Valuating the marine heritage of a land snail. Sci Total Environ. 2018; 648:561-571. DOI: 10.1016/j.scitotenv.2018.07.426. View

Cai L, Satoh M, Tohyama C, Cherian M . Metallothionein in radiation exposure: its induction and protective role. Toxicology. 1999; 132(2-3):85-98. DOI: 10.1016/s0300-483x(98)00150-4. View

10.

Berger B, Hunziker P, Hauer C, Birchler N, Dallinger R . Mass spectrometry and amino acid sequencing of two cadmium-binding metallothionein isoforms from the terrestrial gastropod Arianta arbustorum. Biochem J. 1995; 311 ( Pt 3):951-7. PMC: 1136094. DOI: 10.1042/bj3110951. View

11.

Pedrini-Martha V, Koll S, Dvorak M, Dallinger R . Cadmium Uptake, Gene Activation and Structure of Large-Sized Multi-Domain Metallothioneins in the Terrestrial Door Snail (Gastropoda, Clausiliidae). Int J Mol Sci. 2020; 21(5). PMC: 7084494. DOI: 10.3390/ijms21051631. View

12.

Branca J, Pacini A, Gulisano M, Taddei N, Fiorillo C, Becatti M . Cadmium-Induced Cytotoxicity: Effects on Mitochondrial Electron Transport Chain. Front Cell Dev Biol. 2020; 8:604377. PMC: 7734342. DOI: 10.3389/fcell.2020.604377. View

13.

Freedman J, Slice L, Dixon D, Fire A, Rubin C . The novel metallothionein genes of Caenorhabditis elegans. Structural organization and inducible, cell-specific expression. J Biol Chem. 1993; 268(4):2554-64. View

14.

Chabicovsky M, Klepal W, Dallinger R . Mechanisms of cadmium toxicity in terrestrial pulmonates: programmed cell death and metallothionein overload. Environ Toxicol Chem. 2004; 23(3):648-55. DOI: 10.1897/02-617. View

15.

Baumann C, Beil A, Jurt S, Niederwanger M, Palacios O, Capdevila M . Structural Adaptation of a Protein to Increased Metal Stress: NMR Structure of a Marine Snail Metallothionein with an Additional Domain. Angew Chem Int Ed Engl. 2017; 56(16):4617-4622. DOI: 10.1002/anie.201611873. View

16.

Hockner M, Dallinger R, Sturzenbaum S . Nematode and snail metallothioneins. J Biol Inorg Chem. 2011; 16(7):1057-65. DOI: 10.1007/s00775-011-0826-3. View

17.

Romero-Isart N, Vasak M . Advances in the structure and chemistry of metallothioneins. J Inorg Biochem. 2002; 88(3-4):388-96. DOI: 10.1016/s0162-0134(01)00347-6. View

18.

Dvorak M, Lackner R, Niederwanger M, Rotondo C, Schnegg R, Ladurner P . Metal binding functions of metallothioneins in the slug Arion vulgaris differ from metal-specific isoforms of terrestrial snails. Metallomics. 2018; 10(11):1638-1654. DOI: 10.1039/c8mt00215k. View

19.

Hall J, Haas K, Freedman J . Role of MTL-1, MTL-2, and CDR-1 in mediating cadmium sensitivity in Caenorhabditis elegans. Toxicol Sci. 2012; 128(2):418-26. PMC: 3493192. DOI: 10.1093/toxsci/kfs166. View

20.

Wang S, Chu Z, Zhang K, Miao G . Cadmium-induced serotonergic neuron and reproduction damages conferred lethality in the nematode Caenorhabditis elegans. Chemosphere. 2018; 213:11-18. DOI: 10.1016/j.chemosphere.2018.09.016. View