Responsive-to-antagonist1, a Menkes/Wilson disease-related copper transporter, is required for ethylene signaling in Arabidopsis

Ethylene is an important regulator of plant growth. We identified an Arabid opsis mutant, responsive-to-antagonist1 (ran1), that shows ethylene phenoty pes in response to treatment with trans-cyclooctene, a potent receptor anta gonist. Genetic epistasis studies revealed an early requirement for RAN1 in the ethylene pathway. RAN1 was cloned and found to encode a protein with s imilarity to copper-transporting P-type ATPases, including the human Menkes /Wilson proteins and yeast Ccc2p. Expression of RAN1 complemented the defec ts of a ccc2 Delta mutant, demonstrating its function as a copper transport er. Transgenic CaMV 35S::RAN1 plants showed constitutive expression of ethy lene responses, due to cosuppression of RAN1. These results provide an in p lanta demonstration that ethylene signaling requires copper and reveal that RAN1 acts by delivering copper to create functional hormone receptors.