Cationic amino acid transporters (CAT) enhance accumulation and susceptibility to the systemic herbicide L-phosphinothricin

The broad-spectrum herbicide L-phosphinothricin (PPT) irreversibly inhibits glutamine synthetase (GS) activity. Here we present cationic amino acid transporters (CAT) as mediators of PPT accumulation and susceptibility. Comparative analysis of Arabidopsis thaliana, Marchantia polymorpha, rice, and Klebsormidium nitens reveals conserved responses to GS inhibition, with absence of efficient PPT uptake underlying resistance in M. polymorpha. Transcriptomic analysis identifies four candidate transporters in A. thaliana which, when overexpressed in M. polymorpha, confer varying levels of sensitivity corresponding with PPT accumulation. AtCAT1 and AtCAT5 confer the greatest sensitivities and are required for glutamic acid uptake and endogenous nitrogen metabolism in A. thaliana, and PPT susceptibility. Molecular dynamics simulation of AtCAT5 identifies key residues involved in PPT binding, which induce the rotational flexibility of helices H1 and H6 which form an intracellular access tunnel. These findings highlight the natural diversity underlying PPT accumulation and susceptibility, which can guide herbicide resistance management strategies.