Fig. 7: A proposed working model of the WAKL4-NRAMP1 module in controlling Cd uptake and tolerance.

In WT plants, exposure to Cd toxicity triggers the accumulation of WAKL4 protein rapidly through enhancement of WAKL4 transcription and suppression of WAKL4 degradation. This process may involve an unknown E3 ligase to sense or respond to Cd. Then, WAKL4 confers the phosphorylation of NRAMP1 at Tyr488 residue. The phosphorylated NRAMP1Tyr488 further undergoes endocytosis and vacuole-targeted degradation, which may likewise require unknown E3 ligase, thereby restricting Cd uptake and accumulation in plants. This Cd switch mechanism is generally blocked in wakl4 mutants. The constitution of the WAKL4-NRAMP1 signaling pathway allows for effectively regulating plant Cd uptake and tolerance under Cd stress.