Heavy metal pumps and epigenetic regulation of nutrient transport
Heavy metal pumps (P1B ATPases) are omnipresent in all life forms and the most common P-type ATPases in bacteria and archaea. In humans they are represented by ATP7A and ATP7B, the genes of which are affected in the Menkes and Wilson diseases, respectively.
Phylogenetically the P1B subfamily is divided into monovalent (Cu+, Ag+) and divalent (Cu2+, Zn2+, Co2+, Pb2+, Cd2+) ) metal pumps. P1B ATPases serve three purposes:
- provide heavy metals (most commonly Cu and Zn) required for maturation of metalloproteins, which in eukaryotes typically occur in organelles or in the lumen of secretory vesicles; and
- extrude toxic heavy metals across the plasma membrane (both Cu and Zn can be harmful at elevated concentrations); and, in plants,
- redistribute Zn in the plant body by pumping it out of xylem parenchyma cells into the vascular tissue leading from the root to the shoot.
In A. thaliana eight P1B-ATPase genes (heavy metal ATPases 1–8 [HMA1–HMA8]) are present. In concert, HMA pumps control the intricate heavy metal homeostasis of cells and organelles and ascertain that levels are neither too low nor toxic. Heavy metal pumps respond to changes in metal concentrations at both the gene and protein levels. In the close relative to A. thaliana, Arabidopsis halleri, HMA4 is subject to strong regulation at the gene level in response to available Zn.
At the protein level, we have recently demonstrated that HMA4 is equipped with a Zn-sensor able to bind 10 Zn2+ ions simultaneously. Further, we have observed that the transcript level of HMA1 is strongly induced by Zn deficiency. New findings strongly indicate that heavy metal pumps are regulated at a third level, the epigenetic.
- Baekgaard L, Mikkelsen MD, Sørensen DM, Hegelund JN, Persson DP, Mills RF, Yang Z, Husted S, Andersen JP, Buch-Pedersen MJ, Schjoerring JK, Williams LE, Palmgren MG (2010) A combined zinc/cadmium sensor and zinc/cadmium export regulator in a heavy metal pump. J Biol Chem. 285: 31243-52.