ABI1/ABI2-mediated dephosphorylation of NRAMP1 couples ABA signaling to manganese homeostasis

Manganese (Mn) homeostasis, the precise regulation of cellular Mn levels, is crucial for plant growth and is maintained primarily through the transporter NATURAL RESISTANCE-ASSOCIATED MACROPHAGE PROTEIN 1 (NRAMP1). While the kinases responsible for its phosphorylation are well-established, the phosphatases mediating its dephosphorylation remain unidentified. We identify ABI1 and ABI2 as the phosphatases acting on NRAMP1, linking ABA signaling to Mn homeostasis. Mn stresses trigger ABA to inhibit ABI1/2, which may enable NRAMP1 phosphorylation and stress initiation. A feedback loop then appears to induce short-term ABI1/2 reactivation, mediating site-specific dephosphorylation of NRAMP1 at Thr498 (to fine-tune uptake under deficiency) and at Ser20 (to limit endocytosis under toxicity). This dephosphorylation restrains overactivation and contributes to the maintenance of Mn ion balance. Subsequent ABI1/2 attenuation may facilitates long-term adaptation. Collectively, our findings support the ABA-ABI1/2-NRAMP1 axis as a feedback-regulated circuit controlling Mn homeostasis; this work reveals an expanded functional repertoire for ABA-signaling PP2Cs and identifies a targetable module for enhancing crop resilience to Mn stress.