Endoplasmic reticulum localization of Sec12p is achieved by two mechanisms: Rer1p-dependent retrieval that requires the transmembrane domain and Rer1p-independent retention that involves the cytoplasmic domain

The fact that the effect of the TMD is Rerlp-dependent suggests that this is due to the retrieval mechanism. In a previous study, we showed that Rerlp is an integral membrane protein in the Golgi apparatus, most probably residing in the cis region of the Golgi (Sato et al., 1995) . Rerlp could serve for ER localization of Secl2p either by directly sending back the molecule to the ER or by preventing its progression to the later compartments of the Golgi. The role of Rerlp in such retrieval processes is in good agreement with the biochemical observations in this study. On DSD, a chimeric construct whose ER localization is achieved by the Rerlp-dependent effect of the TMD, the rate of al---~6 mannosyl modification is quite fast, unlike Secl2p, whereas that of ctl---~3 mannosyl modification is strictly inhibited. Since the ed---)6 and al---)3 modifications take place in the cis and medial compartments of the Golgi apparatus, respectively (Nakayama et al., 1992; , this observation indicates that DSD is rapidly reaching the cis-Golgi but does not move on to the medial-Golgi because it is returned to the ER (see Fig. 13 ). This has led us to conclude that the signal contained in the TMD is for retrieval.