Localization of TGN38 to the trans-Golgi network: involvement of a cytoplasmic tyrosine-containing sequence

In yeast cells, cytoplasmic sequences also play a role in localization to a late Golgi compartment that may be the functional equivalent of the mammalian TGN. The cytoplasmic domain of dipeptidyl aminopeptidase A (DPAP A), a yeast Golgi peptidase, has been shown to be sufficient for retention of the protein in Golgi structures (Roberts et al., 1992) . Similarly, deletion of the cytoplasmic tail of kex2p, a yeast Golgi pro-hormone processing peptidase, has been shown to result in mislocalization of the protein from a late Golgi compartment (Fuller et al., 1989) , Preliminary observations from our laboratory have indicated that the cytoplasmic domain of a rat kex2p homologue, furin (Misumi et al., 1990) , also has information sufficient for localization to the mammalian Golgi complex (J. S. Humphrey, J. Davidson, and J. S. Bonifacino, unpublished observations). Interestingly, several proteins localized to late compartments of the Golgi complex have potential aromatic amino acid-based motifs (Trowbridge, 1991) that may be involved in late Golgi or TGN localization. These proteins include DPAP A from Saccharomyces cerevisiae (Roberts et al., 1992) ; the kex2p homologues from S. cerevisiae (Fuller et al., 1989) , Kluyveromyces lactis (Tanguy-Rougeau, 1988) , Drosophila melanogaster (Hayflick et al., 1991) , mouse (Hatsuzawa et al., 1990) , rat (Misumi et al., 1990) , and human (van den Ouweland et al., 1990) ; and kexlp from S. cerevisiae (Dmochowska et al., 1987) . Additional mutagenesis studies will be needed to establish whether these cytoplasmic motifs are involved in late Golgi or TGN localization, as is the case for TGN38. If true, it will mean that cytoplasmic motifs are widely used as signals for localization to late Golgi compartments and will raise the possibility that an evolutionarily conserved mechanism exists to recognize such signals.