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

The disruption of TGN localization, but not internalization, by the mutation of R to D demonstrates an apparent fine specificity of the sequence YQRL for TGN localization which has precedent in studies of cytoplasmic signals for sorting to lysosomes and to the basolateral surface of polarized epithelial cells. For instance, most lysosomal integral membrane proteins have a cytoplasmic tyrosine residue that is critical for both lysosomal targeting and internalization (reviewed by Fukuda, 1991) . For the lysosomal protein lgp120, a glycine immediately before the tyrosine residue is essential for targeting to lysosomes at low expression levels, but is dispensable for internalization (Harter and Mellman, 1992) . Similarly, for lysosomal acid phosphatase, mutation of the critical cytoplasmic tyrosine residue to a phenylalanine abrogates basolateral targeting of the enzyme in polarized cells without affecting internalization (yon Figura; cited in Mostov et al., 1992) . Taken together, these observations suggest that cytoplasmic aromatic amino acid-containing motifs can be recognized at more than one point in the secretory and endocytic pathways, with overlapping but distinct specificities. The sequence YQRL probably belongs to a subset of internalization signals that have a specific capability to confer TGN localization.