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

In the present study, we have sought to identify specific sequences that are involved in localizing TGN38 to the TGN, as a first step to examine the molecular mechanisms that determine protein localization and sorting in this compartment. The results of our experiments demonstrate that the cytoplasmic tail of TGN38 can confer TGN localization on another protein which normally resides at the plasma membrane. Thus, this cytoplasmic tail contains information that is not only necessary but also sufficient for TGN localization. The sequence YQRL, near the COOH-terminal end of the cytoplasmic tail, is essential for TGN localization. Overexpression of chimeric proteins containing the TGN38 tail results not only in detection of the chimeras at the cell surface, but also in disappearance of endogenous TGN38 from its normal intracellular location. These observations suggest that, unlike retention in the Golgi stacks, localization to the TGN may be mediated by specific recognition of a cytoplasmic determinant containing a critical tyrosine-based motif.