The cation/H⁺ exchanger OsCAX2 is involved in cadmium uptake and contributes to differential grain cadmium accumulation between Indica and Japonica rice

Rice is a major source of dietary cadmium (Cd), a toxic heavy metal that poses serious threat to human health. How rice takes up and accumulates Cd is not fully understood. Here, we characterize the function of a cation/H⁺ exchanger, OsCAX2, in Cd uptake in roots and Cd accumulation in shoots and grains. OsCAX2 exhibited Cd and calcium (Ca) transport activities when was heterologously expressed in yeast. OsCAX2 was mainly expressed in roots, particularly in lateral roots, and in the exodermis and endodermis of primary roots. OsCAX2 is localized at the plasma membrane. Knockout of OsCAX2 significantly decreased Cd uptake in roots and Cd accumulation in shoots and grains. Knockout of OsCAX2 also decreased the Ca concentration in roots, but not in shoots or grains. Surprisingly, overexpression of OsCAX2 also resulted in a significant decrease in the Cd concentrations in roots and shoots. We further reveal that the variation in the coding sequence of OsCAX2 contributes to differential grain Cd accumulation between two major rice subspecies, Indica and Japonica. Our results demonstrate that OsCAX2 functions in Cd/Ca uptake in roots and could be a useful target for breeding or genetic engineering low Cd rice varieties.