A TYROSINE-BASED MOTIF AND A CASEIN KINASE-II PHOSPHORYLATION SITE REGULATE THE INTRACELLULAR TRAFFICKING OF THE VARICELLA-ZOSTER VIRUS GLYCOPROTEIN-I, A PROTEIN LOCALIZED IN THE TRANS-GOLGI NETWORK

We have studied the intracellular trafficking of the envelope glycopro tein I (gpI) of the varicella-zoster virus, a human herpes virus whose assembly is believed to occur in the trans-Golgi network (TGN) and/or in endocytic compartments, When expressed in HeLa cells in the absenc e of additional virally encoded factors, this type-I membrane protein localizes to the TGN and cycles between this compartment and the cell surface, The expression of gpI promotes the recruitment of the AP-1 Go lgi-specific assembly proteins onto TGN membranes, strongly suggesting that gpI, like the mannose 6-phosphate receptors, can leave the TGN i n clathrin-coated vesicles for subsequent transport to endosomes. Its return from the cell surface to the TGN also occurs through endosomes, The transfer of the gpI cytoplasmic domain onto a reporter molecule s hows that this domain is sufficient to confer TGN localization, Mutati onal analysis of this domain indicates that proper subcellular localiz ation and cycling of gpI depend on two different determinants, a tyros ine-containing tetrapeptide related to endocytosis sorting signals and a cluster of acidic amino acids containing casein kinase II phosphory latable residues, Thus, the VZV gpI and the mannose 6-phosphate recept ors, albeit localized in different intracellular compartments at stead y-state, follow similar trafficking pathways and share similar sorting mechanisms.