Retromer and the dynamin Vps1 cooperate in the retrieval of transmembrane proteins from vacuoles

Endosomes are dynamic organelles that need to combine the ability to successfully deliver proteins and lipids to the lysosome-like vacuole, and recycle others to the Golgi or the plasma membrane. We now show that retromer, which is implicated in retrieval of proteins from endosomes to the Golgi or to the plasma membrane, can act on vacuoles. We explore its function using an assay that allows us to dissect the required cofactors during recycling. We demonstrate that recycling of the transmembrane receptor Vps10 from vacuoles requires the retromer, the dynamin-like Vps1, and the Rab7 GTPase Ypt7. Retromer and Vps1 leave the vacuole together with the cargo, whereas Ypt7 stays behind, in agreement with its regulatory function. Recycled cargo then accumulates at endosomes and later at the Golgi, implying consecutive sorting steps to the final destination. Our data further suggest that retromer and Vps1 are essential to maintain vacuole membrane organization. Taken together, our data demonstrate that retromer can cooperate with Vps1 and the Rab Ypt7 to clear the vacuole of selected membrane proteins