Targeting of protein ERGIC-53 to the ER/ERGIC/cis-Golgi recycling pathway

Localization by protein retrieval is a fundamentally different process. Here, membrane proteins enter budding vesicles and are transported to the next compartment, where they are recognized by a receptor and sorted into vesicles destined for recycling to the compartment of origin (Pelham and Munro, 1993) . Such a process was described for type I membrane proteins of the ER that contain a COOH-terminal di-lysine ER-retrieval signal, KKXX or KXKXX, in their cytoplasmic domain (Jackson et al., 1990) . In mammalian and in yeast cells these proteins can leave the ER and recycle from a post-ER compartment (Jackson et al., 1993; Gaynor et al., 1994; Townsley et al., 1994) . Di-lysine signals were shown to bind coatomer in vitro (Cosson and Letourneur, 1994) and mutations in yeast coatomer subunits effect the intracellular retention of di-lysine proteins in vivo (Letourneur et al., 1994) . These findings support a coatomer-mediated retrieval mechanism for di-lysine ER proteins.