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

The sequence YQRL, identified by our mutagenesis studies as essential for TGN localization, resembles other sequences involved in internalization of cell surface receptors. The internalization signals of the transferrin receptor, mannose-6phosphate receptors, asialoglycoprotein receptor, polymeric immunoglobulin receptor, and others are all tetrapeptides having an aromatic residue in the first position and a bulky hydrophobic residue in the fourth position of the sequence (reviewed by Trowbridge, 1991) . These aromatic amino acid-based motifs have been proposed to form a tight turn structure that acts as a conformational signal for endocytosis (Co[lawn et al., 1990) . Our analysis of the cytoplasmic sequence of TGN38 using the algorithm of Chou and Fasman (1978) , predicted a high probability of a B-turn in the region around Y333. These considerations led us to test whether the sequence YQRL could also function as an internalization signal.