2.A.55.2.4
The major root plasma membrane high affinity Me²⁺(Fe²⁺, Co²⁺. Mn²⁺, Cd²⁺) uptake transporter, NRAMP-1 (also called NRAMP1 and NRAMP-6) is stimulated by Mn²⁺ deficiency) (Cailliatte et al., 2010).  In silico analyses of plant NRAMPs have been performed  using NRAMP1 as the query sequence (Vatansever et al. 2016). Cd²⁺ stress induces Ca²⁺ signals in Arabidopsis roots. The calcium-dependent protein kinases, CPK21 and CPK23, interact with the Cd transporter, NRAMP6/NRAMP1, through a variety of protein interactions. CPK21/23 phosphorylate NRAMP6 primarily at Ser489 and Thr505 to inhibit the Cd²⁺ transport activity of NRAMP6, thereby improving the Cd tolerance of plants (Zhang et al. 2022). Two calcineurin B-like proteins, CBL1/9, and their interacting kinase CIPK23, positively regulate the tolerance of Mn toxicity in Arabidopsis. The cbl1 cbl9 double mutant and cipk23 mutants exhibited high-Mn-sensitive phenotypes, which manifested as decreased primary root length, biomass, and chlorophyll concentration, as well as higher accumulation of Mn. In addition, CIPK23 interacted with and phosphorylated the Mn transporter NRAMP1 primarily at Ser20/22, and thereby induced clathrin-mediated endocytosis of NRAMP1 to reduce its distribution in the plasma membrane and enhance plant tolerance to Mn toxicity. Hence, the CBL1/9-CIPK23-NRAMP1 module regulates the tolerance to high-Mn toxicity and provides insight into a mechanism of tolerance of plants to Mn toxicity (Zhang et al. 2023).