Worms take the ‘phyto’ out of ‘phytochelatins’

Vatamaniuk, Olena K.; Bucher, Elizabeth A.; Ward, James Thomas; Rea, Philip A.

doi:10.1016/s0167-7799(01)01873-x

Cited by 45 publications

(25 citation statements)

References 21 publications

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“…Domain comparisons among the half-molecule ABC transporters in the protein databases of other animals disclose transporters that are HMT-1-like (for instance, CG4225 from Drosophila and mammalian mitochondrial ABC protein 3 (MTABC3) from humans). This would not be expected from what is known of SpHMT1, because Drosophila and humans do not deploy a PC-dependent pathway for heavy metal detoxification (30). Three explanations capable of reconciling what ostensibly is a contradiction might follow from these findings and from the results of studies implicating mammalian mitochondrial ABC protein 3 in iron homeostasis (31).…”

Section: Discussionmentioning

confidence: 99%

CeHMT-1, a Putative Phytochelatin Transporter, Is Required for Cadmium Tolerance in Caenorhabditis elegans

Vatamaniuk

Bucher²,

Sundaram

et al. 2005

Journal of Biological Chemistry

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Phytochelatins (PCs), (␥-Glu-Cys) n Gly polymers that were formerly considered to be restricted to plants and some fungal systems, are now known to play a critical role in heavy metal (notably Cd 2؉ ) detoxification in Caenorhabditis elegans. In view of the functional equivalence of the gene encoding C. elegans PC synthase 1, ce-pcs-1, to its homologs from plant and fungal sources, we have gone on to explore processes downstream of PC fabrication in this organism. Here we describe the identification of a half-molecule ATP-binding cassette transporter, CeHMT-1, from C. elegans with an equivalent topology to that of the putative PC transporter SpHMT-1 from Schizosaccharomyces pombe. At one level, Ce-HMT-1 satisfies the requirements of a Cd . These results and those from our previous investigations of the requirement for PC synthase for heavy metal tolerance in C. elegans demonstrate PC-dependent, HMT-1-mediated heavy metal detoxification not only in S. pombe but also in some invertebrates while at the same time indicating that the action of Ce-HMT-1 does not depend exclusively on PC synthesis.The toxicity of supraoptimal levels of the essential heavy metals copper and zinc and of trace or higher levels of the nonessential heavy metals cadmium, arsenic, mercury, and lead is thought to result from the displacement of endogenous co-factors from their cellular binding sites, thiol-capping of essential proteins and peptides, and promotion of the formation of reactive oxygen species (1). In humans, the repercussions of heavy metal exposure can range from acute poisoning to progressive kidney, liver, and lung dysfunction and, in some instances, cancer. Although its true clinical and epidemiological significance remains to be determined, chronic exposure to heavy metals is often associated with muscular and neurological degenerative conditions reminiscent of muscular dystrophy, multiple sclerosis, Alzheimer disease, and Parkinson disease (2-4).Three classes of heavy metal-binding peptides are known to participate in the homeostasis and detoxification of heavy metals in most animals. These are the ubiquitous thiol tripeptide glutathione (GSH), a family of small (4 -8 kDa) cysteine-rich proteins termed metallothioneins, and several higher molecular mass albeit sequence-unrelated metal-binding proteins. In all of the plants studied and in some fungi (as exemplified by Schizosaccharomyces pombe and Candida glabrata) and some animals (as exemplified by the model nematode Caenorhabditis elegans), a third class of cysteine-rich peptides termed phytochelatins (PCs) 1 has also been shown to be involved in heavy metal detoxification.PCs, which constitute a family of short-chain heavy metalbinding peptides with the general structure (␥-EC) n Xaa, where n ϭ 2-11, are derived from GSH and related thiols in a ␥-glutamylcysteinyl transpeptidation reaction catalyzed by phytochelatin synthases (EC 2.3.2.15) (1,5,6). It is now almost 15 years since the partial purification of the enzyme capable of catalyzing PC synthesis (5), yet it is onl...

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Section: Discussionmentioning

confidence: 99%

CeHMT-1, a Putative Phytochelatin Transporter, Is Required for Cadmium Tolerance in Caenorhabditis elegans

Vatamaniuk

Bucher²,

Sundaram

et al. 2005

Journal of Biological Chemistry

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“…PCs are low-molecular weight peptides synthesized from glutathione by the enzyme PC synthase. They were considered to be plant-specific until the recent isolation of a phytochelatin synthase and a phytochelatin transporter gene from Caenorhabditis elegans (Vatamaniuk et al, 2002(Vatamaniuk et al, , 2005. Also for earthworms and chironomids a role for PCs is suggested (Cobbett & Goldsbrough, 2002).…”

Section: Mechanisms Of the Cadmium-induced Stress Responsementioning

confidence: 99%

Molecular mechanisms of heavy metal tolerance and evolution in invertebrates

Janssens¹,

Roelofs²,

Straalen³

2009

Insect Science

144

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Following the genomics revolution, our knowledge of the molecular mechanisms underlying defenses against stress has been greatly expanded. Under strong selective pressure many animals may evolve an enhanced stress tolerance. This can be achieved by altering the structure of proteins (through mutations in the coding regions of genes) or by altering the amount of protein (through changes in transcriptional regulation). The latter type of evolution can be achieved by substitutions in the promoter of the gene of interest (cisregulatory change) or by altering the structure or amount of transcriptional regulator proteins (trans-regulatory change). The metallothionein system is one of the best studied stress response systems in the context of heavy metals. Metallothionein expression is assumed to be regulated by metal transcription factor 1 (MTF-1); however, up to now the involvement of MTF-1 has only been proven for some vertebrates and Drosophila. Data on invertebrates such as nematodes and earthworms suggest that other mechanisms of metallothionein induction may be present. A detailed study of Cd tolerance was done for a species of soilliving springtail, Orchesella cincta. The metallothionein gene of this species is overexpressed in metal-exposed field populations. Analysis of the metallothionein promoter has demonstrated extensive polymorphisms that have a functional significance, as shown in bioreporter assays. In a study comparing 20 different populations, the frequency of a high-expresser promoter allele was positively correlated with the concentration of metals in soil, especially Cd. The springtail study shows that cis-regulatory change of genes involved in the cellular stress response may contribute to evolution of metal tolerance.

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“…It is exhilarating to think that the involvement of PCs in the detoxification of heavy metals in animals had not been even cursorily mentioned or speculated on in the literature before the discovery, which owes its origins to fundamental research on plants, of CePCS1 (Vatamaniuk et al, 2002). By the same token, it is salutatory to learn that while other gene products have been inferred to contribute to Cd 21 tolerance in C. elegans, CePCS1 is actually the first for which there is a firm biochemical basis for the effects seen at the level of the whole organism.…”

Section: From Weeds To Wormsmentioning

confidence: 99%