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

Yeast Sec12p is a type II transmembrane glycoprotein and is essential for formation of transport vesicles from the ER (Nakano et al., 1988; d'Enfert et al., 1991; Rexach and Schekman, 1991; Oka and Nakano, 1994) . Most of Secl2p is localized to the ER in the steady state (Nakano et al., 1988; Nishikawa and Nakano, 1993) and not detected on the purified transport vesicles (T. Oka and A. Nakano, unpublished; Barlowe et al., 1994) . However, a significant portion of Sec12p receives ed--+6 mannose modification on its N-linked oligosaccharide, which takes place in the early Golgi (Nakano et al., 1988; d'Enfert et al., 1991; Nishikawa and Nakano, 1993) . Based on these observations, we have proposed that the ER localization of Secl2p involves two different mechanisms: static retention in the ER and dynamic retrieval from the early Golgi. Secl2p molecules are largely excluded from the transport vesicles during budding from the ER, and those escaping from this retention are sent back from the Golgi to the ER by the retrograde pathway (Nishikawa and Nakano, 1993; Sato et al., 1995) .