Phosphorylation-Regulated Cleavage of ETHYLENE INSENSITIVE2 Mediates Hormone Signaling from the Endoplasmic Reticulum to the Nucleus

Ethylene gas is essential for many developmental processes and stress responses in plants. ETHYLENE INSENSITIVE2 (EIN2), an NRAMP-homologous integral membrane protein, plays an essential role in ethylene signaling but its function remains enigmatic. Here we report that phosphorylation-regulated proteolytic processing of EIN2 triggers its endoplasmic reticulum (ER)-nucleus translocation, which is essential for hormone signaling and response in Arabidopsis. Without ethylene, or in hormone receptors mutants, ER-tethered EIN2 shows CTR1 kinase-dependent phosphorylation. Ethylene exposure triggers dephosphorylation and proteolytic cleavage, resulting in rapid nuclear translocation of a carboxyl-terminal EIN2 fragment (C’). Plants containing mutations that mimic EIN2 dephosphorylation, or inactivate CTR1, show constitutive cleavage and nuclear localization of EIN2-C’, and EIN3/EIL1-dependent activation of ethylene responses. These findings uncover a mechanism of subcellular communication whereby ethylene gas stimulates rapid phosphorylation-dependent cleavage and nuclear movement of the EIN2-C’ peptide, thus linking hormone perception and signaling components located in the ER with nuclear-localized transcriptional regulators.