Retention of p63 in an ER-Golgi intermediate compartment depends on the presence of all three of its domains and on its ability to form oligomers

It is currently believed that secretory proteins are transported by a default pathway while resident proteins are selectively retained in individual organelles by means of specific signals (Pfeffer and Rothman, 1987; Wieland et al., 1987; Karrenbauer et al., 1990) . Two types of signais, which mediate either the retention or the retrieval of proteins, have been identified to date. A variety of lumenal ER proteins are retained in the cell by means of a COOH-terminal tetrapeptide (KDEL) or related sequence (Munro and Pelham, 1987; reviewed by Pelham, 1989 Pelham, , 1990 ) that allows retrievai of the proteins from a post-ER site by means of KDEL receptors Pelham, 1990, 1992) . A group of type I transmembrane proteins of the ER are also retained in this or-ganelle by a retrieval mechanism (Jackson et al., 1993) . These proteins contain cytoplasmic sequences consisting of two lysine residues positioned three and four or five residues from the COOH terminus (KKXX or KXKXX, where X can be almost any amino acid) (Jackson et ai., 1990; Shin et ai., 1991) . Recycling of these proteins is believed to occur from multiple post-ER locations along the secretory pathway (Jackson et ai., 1993) . In addition, retrieval has been suggested to be the mechanism by which the integral membrane protein TGN38 is targeted to the TGN (Bos et ai., 1993; Humphrey et al., 1993) . TGN38 possesses a tyrosine-containing motif within its cytoplasmic tail that is both necessary and sufficient for TGN localization (Bos et ai., 1993; Humphrey et ai., 1993; Wong and Hong, 1993) . In contrast to these examples, localization of Golgi proteins is achieved by retention rather than retrieval. The retention of several Golgi proteins has been shown to depend primarily on their single transmembrane segment with some additional contribution to retention by the sequences just adjacent to those membrane anchors (Nilsson et ai., 1991; Swift and Machamer, 1991; Machamer et al., 1993) . In the case of the c~ 2,6-siaiyltransferase, the cytoplasmic and lumenal sequences flanking the transmembrane segment appear to be the crucial elements for retention rather than the transmembrane segment itself (Munro, 1991; Dahdal and Colley, 1993) . It has been postulated that resident Golgi proteins oligomerize in the Golgi apparatus upon recognition of identical or related proteins, forming a complex of sufficient size to prevent entry into transport vesicles (Machamer, 1991; Nilsson et al., 1991 Nilsson et al., , 1993 Nilsson et al., , 1994 . Recently, oligomerization of a chimeric protein containing the first membrane-spanning domain of the M glycoprotein of avian coronavirus has been correlated to its retention in the Golgi apparatus (Weisz et al., 1993) .