RETRIEVAL OF TGN PROTEINS FROM THE CELL-SURFACE REQUIRES ENDOSOMAL ACIDIFICATION

TGN38 is a protein of unknown function located in the trans-Golgi netw ork (TGN) of mammalian cells. Its intracellular distribution is mainta ined by it being continuously retrieved from the plasma membrane. In t his paper we show that when cells are treated,vith agents such as chlo roquine which neutralize acidic organelles, the movement of TGN38 alon g the endocytic pathway is blocked. The same effect is observed with a second TGN protein, the protease furin. We show that the cytoplasmic tail of furin is sufficient to confer a chloroquine-sensitive TGN loca lization on a heterologous protein. These results imply that the inter nal pH of endosomes affects sorting processes mediated by signals in t he cytoplasmic portion of proteins and have implications for the role of acidification in endosomal function.