Lysine-Histidine Transporter 4 (AtLHT4) facilitates the uptake of narciclasine, a bioactive alkaloid, in Arabidopsis

Members of the Lysine-Histidine Transporter (LHT) family are known to mediate amino acid uptake, nitrogen acquisition, and responses to abiotic and biotic stresses in plants. However, their potential roles in responding to other plant-derived metabolites remain largely unexplored. Here, we identify AtLHT4 as a key contributor to Arabidopsis sensitivities to narciclasine (NCS), a bioactive alkaloid derived from the Amaryllidaceae family. Through genetic mapping and functional analyses, we found that loss of AtLHT4 function significantly enhances plant resistance to NCS, while mutations in other AtLHT members have no detectable effect. LC-MS analysis showed that lht4 mutants accumulate ∼70 % less NCS in roots after 4 h of exposure, whereas AtLHT4 overexpression increases NCS accumulation. Yeast cells heterologously expressing AtLHT4 also accumulated higher intracellular concentrations of NCS compared to vector controls, confirming its role in mediating NCS uptake. Spatial expression analysis revealed that AtLHT4 is predominantly expressed in seeds, the root meristematic zone, vascular tissues, floral receptacles, and silique ends, suggesting potential roles in root growth regulation and NCS redistribution. Notably, exogenous application of specific amino acids-including Gly, Glu, Asp, Phe, Asn, and Arg-partially or fully alleviated NCS-induced root growth inhibition in both wild-type and lht4-2 seedlings, indicating possible interactions between amino acid and alkaloid signaling or uptake pathways. Together, our findings uncover a specific role of AtLHT4 in alkaloid uptake and expand the known functional repertoire of the LHT family beyond amino acid transport in plants.