The squash gain-of-function mutant etr2b disrupts the ethylene-binding domain of ethylene receptor CpETR2B, conferring partial ethylene insensitivity, changes in flower and fruit development, and enhanced salt tolerance. In this paper, we found that etr2b also confers a growth advantage as well as a physiological and metabolomic response that make the mutant better adapted to drought. Mutant plants had a higher root and leaf biomass than WT under both well-watered and drought conditions, but the reduction in growth parameters in response to drought was similar in WT and etr2b. Water deficit reduced all gas-exchange parameters in both WT and etr2b, but under moderate drought the mutant increased photosynthesis rate in comparison with control conditions, and showed a higher leaf CO concentration, transpiration rate, and stomata conductance than WT. The response of etr2b to drought indicates that ethylene is a negative regulator of plant growth under both control and drought. Since etr2b increased ABA content in well-watered plant, but prevented the induction of ABA production in response to drought, it is likely that the etr2b response under drought is not mediated by ABA. A H NMR metabolomic analysis revealed that etr2b enhances the accumulation of osmolytes (soluble sugars and trigonelline), unsaturated and polyunsaturated fatty acids, and phenolic compounds under drought, concomitantly with a reduction of malic- and fumaric-acid. The role of CpETR2B and ethylene in the regulation of these drought-protective metabolites is discussed.

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