Anuj Sharma - Detoxification of multiple heavy metals by a half-molecule ABC transporter, HMT-1, and coelomocytes of Caenorhabditis elegans.

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      Developing methods for protecting organisms in metal-polluted   environments is contingent upon our understanding of cellular   detoxification mechanisms. In this regard, half-molecule   ATP-binding cassette (ABC) transporters of the HMT-1 subfamily   are required for cadmium (Cd) detoxification. HMTs have conserved   structural architecture that distinguishes them from other ABC   transporters and allows the identification of homologs in genomes   of different species including humans. We recently discovered   that HMT-1 from the simple, unicellular organism,   Schizosaccharomyces pombe, SpHMT1, acts independently of   phytochelatin synthase (PCS) and detoxifies Cd, but not other   heavy metals. Whether HMTs from multicellular organisms confer   tolerance only to Cd or also to other heavy metals is not known.


      Using molecular genetics approaches and functional in vivo assays   we showed that HMT-1 from a multicellular organism,   Caenorhabditis elegans, functions distinctly from its S. pombe   counterpart in that in addition to Cd it confers tolerance to   arsenic (As) and copper (Cu) while acting independently of pcs-1.   Further investigation of hmt-1 and pcs-1 revealed that these   genes are expressed in different cell types, supporting the   notion that hmt-1 and pcs-1 operate in distinct detoxification   pathways. Interestingly, pcs-1 and hmt-1 are co-expressed in   highly endocytic C. elegans cells with unknown function, the   coelomocytes. By analyzing heavy metal and oxidative stress   sensitivities of the coelomocyte-deficient C. elegans strain we   discovered that coelomocytes are essential mainly for   detoxification of heavy metals, but not of oxidative stress, a   by-product of heavy metal toxicity.


      We established that HMT-1 from the multicellular organism confers   tolerance to multiple heavy metals and is expressed in liver-like   cells, the coelomocytes, as well as head neurons and intestinal   cells, which are cell types that are affected by heavy metal   poisoning in humans. We also showed that coelomocytes are   involved in detoxification of heavy metals. Therefore, the   HMT-1-dependent detoxification pathway and coelomocytes of C.   elegans emerge as novel models for studies of heavy   metal-promoted diseases.

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