Heterologous Expression of a Mammalian ABC Transporter in Plant and its Application to Phytoremediation

Abstract

Mammalian ATP-binding cassette (ABC) transporters involved in the multidrug-resistance of cancer cells can efflux cytotoxic compounds that show a wide variety of chemical structures and biological activities. Human multidrug resistance-associated protein (hMRP1) is one of the most intensively studied ABC transporters and many substrates have been identified, including both organic and inorganic compounds. In an attempt at novel ‘transport engineering’ using hMRP1 as a molecular pump, we established transgenic tobacco plants that showed clear resistance to cadmium and daunorubicin, although they were not resistant to etoposide, another known substrate of hMRP1. When expressed in tobacco cells, hMRP1 protein was localized at vacuolar membrane, while members of the MRP family are localized at plasma membrane in mammalian cells to reduce the cellular accumulation of various drugs. Thus, the hMRP1-expressing tobacco cells were able to take up these substrates across the tonoplast and sequestrate them in the vacuolar matrix. These results suggest that it may be possible to use the transgenic tobacco in phytoremediation, where a single transformation with an ABC transporter with broad substrate specificity should be effective for extracting various environmental pollutants including both organic and inorganic compounds, and accumulate them in the plant body. This should be advantageous for the remediation of a complex polluted environment, which is commonly found in the real world.