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

EMBO J. 1996 Nov 15;15(22):6096-110.


We have studied the intracellular trafficking of the envelope glycoprotein 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 absence 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 Golgi-specific assembly proteins onto TGN membranes, strongly suggesting that gpI, like the mannose 6-phosphate receptors, can leave the TGN in 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 shows that this domain is sufficient to confer TGN localization. Mutational analysis of this domain indicates that proper subcellular localization and cycling of gpI depend on two different determinants, a tyrosine-containing tetrapeptide related to endocytosis sorting signals and a cluster of acidic amino acids containing casein kinase II phosphorylatable residues. Thus, the VZV gpI and the mannose 6-phosphate receptors, albeit localized in different intracellular compartments at steady-state, follow similar trafficking pathways and share similar sorting mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Protein Complex gamma Subunits
  • Amino Acid Sequence
  • Binding Sites
  • Brefeldin A
  • Casein Kinase II
  • Cyclopentanes / pharmacology
  • Endosomes / metabolism
  • Furin
  • Gene Expression Regulation, Viral / genetics
  • Glycoproteins*
  • Golgi Apparatus / chemistry*
  • Golgi Apparatus / metabolism
  • HeLa Cells
  • Humans
  • Membrane Glycoproteins / analysis
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins / metabolism
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Sorting Signals / metabolism
  • Protein-Serine-Threonine Kinases / metabolism*
  • Receptor, IGF Type 2 / metabolism
  • Recombinant Fusion Proteins
  • Subtilisins / analysis
  • Subtilisins / metabolism
  • Viral Envelope Proteins / metabolism*


  • Adaptor Protein Complex gamma Subunits
  • Cyclopentanes
  • Glycoproteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • Protein Sorting Signals
  • Receptor, IGF Type 2
  • Recombinant Fusion Proteins
  • TGOLN2 protein, human
  • Viral Envelope Proteins
  • glycoprotein E, varicella-zoster virus
  • Brefeldin A
  • Casein Kinase II
  • Protein-Serine-Threonine Kinases
  • Subtilisins
  • Furin