The chronic exposure of humans to heavy metals, either occupational or from food and air, leads to their accumulation in tissues and causes various diseases, including neurodegenerative conditions, dysfunction of vital organs, and cancer. Protecting and detoxifying organisms in metal-polluted environments are contingent on our understanding of the effective cellular detoxification mechanisms. Our past studies have established that
pcs-1 and
hmt-1, encoding phytochelatin (PC) synthase and a half molecule ATP binding cassette (ABC) transporter respectively, are acutely required for the detoxification of Cd2+, but despite what was thought previously, do not act in concert in heavy metal detoxification (Vatamaniuk et al 2001, 2005). Here, we show that in addition to Cd2+,
pcs-1 and
hmt-1 confer tolerance to As3+ and Cu2+. Consistent with the notion that
pcs-1 and
hmt-1 operate in distinct metal detoxification pathways,
pcs-1;
hmt-1 double mutants are more sensitive to these metals than
pcs-1 or
hmt-1 single mutants, and are expressed in distinct tissues:
hmt-1 is expressed in intestinal cells and head and tail neurons, whereas
pcs-1 is expressed in pharyngeal grinder, pharyngeal-intestinal valve, somatic and vulval muscles. Interestingly,
pcs-1 and
hmt-1 are co-expressed in coelomocytes. This finding raised the intriguing possibility that coelomocytes are involved in heavy metal detoxification. We tested this hypothesis, by analyzing the heavy metal sensitivity of the coelomocyte-deficient mutant strain, NP717 (from Dr. H. Fares laboratory, University of Arizona). In doing so we established that NP717 worms have increased sensitivity to Cd2+and Cu2+. After 4.5 days of culturing at 200C 100% of N2 worms reached adult stage regardless whether cultured on the medium with or without 50 mM CdCl2 or 200 mM CuCl2. NP717 worms have reached adults stage on the medium devoid of heavy metals as well. In contrast, when grown in the presence of Cd2+ or Cu2+, 54% and 63% of NP717 respectively were delayed at early-developmental stages. These worms either died, not being able to reach an adult stage, or, died shortly after becoming adults and gave none or fewer progeny. These data demonstrate that coelomocytes, the functions of which in worms have not been well-understood, play an essential role in heavy metal detoxification.