LUMENAL AND TRANSMEMBRANE DOMAINS PLAY A ROLE IN SORTING TYPE-I MEMBRANE-PROTEINS ON ENDOCYTIC PATHWAYS

Previous studies have shown that when the cytosolic domains of the typ e I membrane proteins TGN38 and lysosomal glycoprotein 120 (lgp120) ar e added to a variety of reporter molecules, the resultant chimeric mol ecules are localized to the trans-Golgi network (TGN) and to lysosomes , respectively. Ln the present study we expressed chimeric constructs of rat TGN38 and rat lgp120 in HeLa cells. We found that targeting inf ormation in the cytosolic domain of TGN38 could be overridden by the p resence of the lumenal and transmembrane domains of lgp120. In contras t, the presence of the transmembrane and cytosolic domains of TGN38 wa s sufficient to deliver the lumenal domain of lgp120 to the trans-Golg i network. On the basis of steady-state localization of the various ch imeras and antibody uptake experiments, we propose that there is a hie rarchy of targeting information in each molecule contributing to sorti ng within the endocytic pathway. The lumenal and cytosolic domains of lgp120 contribute to sorting and delivery to lysosomes, whereas the tr ansmembrane and cytosolic domains of TGN38 contribute to sorting and d elivery to the trans-Golgi network.