title: HCMV-encoded glycoprotein M (UL100) interacts with Rab11 effector protein FIP4.
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.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, CHB160, Birmingham, AL 35233, USA.
authors.forename: Magdalena A
authors.initials: MA
authors.lastname: Krzyzaniak
authors.forename: Michael
authors.initials: M
authors.lastname: Mach
authors.forename: William J
authors.initials: WJ
authors.lastname: Britt
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003587:Cytomegalovirus / Q000378:metabolism* / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism / Q000821:virology; D004591:Electrophoresis, Polyacrylamide Gel; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000821:virology; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D036681:Fluorescence Recovery After Photobleaching; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D021381:Protein Transport; D014162:Transfection; D020798:Two-Hybrid System Techniques; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; C439063:RAB11FIP3 protein, human; C470424:RAB11FIP4 protein, human; C095281:UL100 protein, Cytomegalovirus; D014759:Viral Envelope Proteins