Oligomerization of a membrane protein correlates with its retention in the Golgi complex

Dr. Ann M. Swifts current address is Smithkline Beecham Pharmaceuticals, Philadelphia, PA. 1992). When cDNA encoding the M protein is expressed in animal cells, the protein is targeted to the cis-Golgi (Machamer et al., 1990) . Structurally, the IBV M protein consists of a short glycosylated amino-terminal domain, three membrane-spanning domains, and a long carboxyterminal cytoplasmic domain. The first membrane-spanning domain (ml) of the M glycoprotein is sufficient to retain this protein in the Golgi (Machamer and Rose, 1987) . Furthermore, the ml domain can confer Golgi localization to a wellcharacterized plasma membrane protein (the G protein of vesicular stomatitis virus, or VSV G). VSV G is a type I membrane protein which is cotranslationally inserted into the ER, where it forms homotrimers. It is then rapidly transported through the Golgi complex (as determined by the kinetics of N-linked oligosaccharide processing) and delivered to the plasma membrane (for review see Doms et al., 1993) . When the membrane-spanning domain of VSV G is replaced with the ml domain of IBV M, the resulting chimera (Gml, see Fig. 1 ) is retained in the Golgi complex (Swift and Machamer, 1991) . Extensive mutagenesis suggests that at least four specific amino acids in the ml domain are critical for Golgi retention of Gml: asparagine 465, threonines 469 and 476, and glutamine 480 (Machamer et al., 1993) . Interestingly, these residues form an uncharged polar face along one side of the alpha helix predicted for ml. The polar nature of this face of the helix suggests that protein-protein interactions along this face may mediate Golgi retention of Gml.