SEQUENCE AND OVEREXPRESSION OF GPP130 GIMPC - EVIDENCE FOR SATURABLE PH-SENSITIVE TARGETING OF A TYPE-II EARLY GOLGI MEMBRANE-PROTEIN/

It is thought that residents of the Golgi stack are localized by a ret ention mechanism that prevents their forward progress. Nevertheless, s ome early Golgi proteins acquire late Golgi modifications. Herein, we describe GPP130 (Golgi phosphoprotein of 130 kDa), a 130-kDa phosphory lated and glycosylated integral membrane protein localized to the cis/ medial Golgi. GPP130 appears to be the human counterpart of rat Golgi integral membrane protein, cis (GIMPc), a previously identified early Golgi antigen that acquires late Golgi carbohydrate modifications. The sequence of cDNAs encoding GPP130 indicate that it is a type II membr ane protein with a predicted molecular weight of 81,880 and an unusual ly acidic lumenal domain. On the basis of the alignment with several r od-shaped proteins and the presence of multiple predicted coiled-coil regions, GPP130 may form a flexible rod in the Golgi lumen. In contras t to the behavior of previously studied type II Golgi proteins, overex pression of GPP130 led to a pronounced accumulation in endocytotic ves icles, and endogenous GPP130 reversibly redistributed to endocytotic v esicles after chloroquine treatment. Thus, localization of GPP130 to t he early Golgi involves steps that are saturable and sensitive to lume nal pH, and GPP130 contains targeting information that specifies its r eturn to the Golgi after chloroquine washout. Given that GIMPc acquire s late Golgi modifications in untreated cells, it seems likely that GP P130/GIMPc continuously cycles between the early Golgi and distal comp artments and that an unidentified retrieval mechanism is important for its targeting.