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

The identification of transmemhrane signals for protein retention in the Golgi stacks (reviewed by Machamer, 1991) represented a significant advance in the understanding of the organization of the Golgi complex and, in a more general sense, imphcated a new mechanism for protein localization within the secretory pathway. Our observations that the cytoplasmic domain of TGN38 contains sufficient information for localization to the TGN demonstrates the existence of a second mechanism operating to localize proteins within the Golgi complex that depends on cytoplasmic rather than transmembrane determinants. The two mechanisms differ not only in the topological domain harboring the localization signal, but also in the characteristics of the localization process. The available evidence indicates that overexpression of proteins normally localized in the Golgi stacks results in their increased detection in the ER but not at the plasma membrane (Munro, 1991; Nilsson et al., 1991; Moremen and Robbins, 1991; Colley et al., 1992) . This is in contrast to TGN-localized proteins which when overexpressed appear at the cell surface and in cytoplasmic vesicles (Luzio et al., 1990; this study) . Although the generality of these observations will have to be assessed for other TGN proteins, the present data reinforce the idea that the Golgi stacks and the TGN are intrinsically different in structure, dynamics and function (Klansner et al., 1992; Mellman and Simons, 1992; Rothman and Orci, 1992) .