HCMV-encoded glycoprotein M (UL100) interacts with Rab11 effector protein FIP4

Traffic. 2009 Oct;10(10):1439-57. doi: 10.1111/j.1600-0854.2009.00967.x.

Abstract

The envelope of human cytomegalovirus (HCMV) consists of a large number of glycoproteins. The most abundant glycoprotein in the HCMV envelope is the glycoprotein M (UL100), which together with glycoprotein N (UL73) form the gM/gN protein complex. Using yeast two-hybrid screening, we found that the gM carboxy-terminal cytoplasmic tail (gM-CT) interacts with FIP4, a Rab11-GTPase effector protein. Depletion of FIP4 expression in HCMV-infected cells resulted in a decrease in infectious virus production that was also associated with an alteration of the HCMV assembly compartment (AC) phenotype. A similar phenotype was also observed in HCMV-infected cells that expressed dominant negative Rab11(S25N). Recently, it has been shown that FIP4 interactions with Rab11 and additionally with Arf6/Arf5 are important for the vesicular transport of proteins in the endosomal recycling compartment (ERC) and during cytokinesis. Surprisingly, FIP4 interaction with gM-CT limited binding of FIP4 with Arf5/Arf6; however, FIP4 interaction with gM-CT did not prevent recruitment of Rab11 into the ternary complex. These data argued for a contribution of the ERC during cytoplasmic envelopment of HCMV and showed a novel FIP4 function independent of Arf5 or Arf6 activity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • Chlorocebus aethiops
  • Cytomegalovirus / metabolism*
  • Cytomegalovirus / physiology
  • Cytoplasm / metabolism
  • Cytoplasm / virology
  • Electrophoresis, Polyacrylamide Gel
  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum / virology
  • Fibroblasts / metabolism
  • Fibroblasts / virology
  • Fluorescence Recovery After Photobleaching
  • Humans
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Polymerase Chain Reaction
  • Protein Binding
  • Protein Transport
  • Transfection
  • Two-Hybrid System Techniques
  • Viral Envelope Proteins / biosynthesis
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism*
  • Virus Replication

Substances

  • Carrier Proteins
  • Membrane Proteins
  • RAB11FIP3 protein, human
  • RAB11FIP4 protein, human
  • UL100 protein, Cytomegalovirus
  • Viral Envelope Proteins