Strigolactones and antifungals induce internalization of major facilitator superfamily transporters.

Abstract

The major facilitator superfamily (MFS) is a diverse class of selective transporters that move a range of substrates across membranes. Despite their central role in cellular homeostasis, chemically perturbing MFS transporters is challenging. Here, we elucidate how the plant hormone, strigolactone (SL), internalizes the yeast MFS phosphate transporter, Pho84, and discover that the agricultural fungicide, chlorothalonil, also interacts with the SL allosteric binding site to cause Pho84 internalization. This piggybacking mechanism for chlorothalonil not only has agricultural applications but also explains why yeast MFS deletion lines show decreased sensitivity to various small molecule perturbagens. Deletion of the MFS inositol transporter, ITR1, for example, results in resistance to specific antifungal azoles. We demonstrate that the Itr1 protein is internalized by these antifungals. These findings propose a new paradigm by which small molecules regulate MFS trafficking and offer new insights to identify drugs targeting MFS transporters.