Dissociation and reassociation of oligomeric viral glycoprotein subunits in the endoplasmic reticulum.
The vesicular stomatitis virus (VSV) glycoprotein (G) forms noncovalently linked trimers in the endoplasmic reticulum (ER) prior to transport to the cell surface. Here we examined the formation of heterotrimers between wild-type and mutant subunits that were retained in the ER by C-terminal retention signals. When G protein was coexpressed with mutant subunits that formed trimers at the wild-type rate and were transported from the ER at the wild-type rate, heterotrimers were readily detected. In contrast, when G protein was coexpressed with mutant subunits that formed trimers at the wild-type rate, but were retained in the ER, heterotrimers were not detected unless transport of the wild-type molecules from the ER was blocked. After removal of transport block, the heterotrimers then dissociated and reassorted to homotrimers of the mutant protein that were retained in the ER and wild-type trimers that were transported to the cell surface. These and other results presented here indicate that there is an equilibrium between G protein trimers and monomers in vivo, at least in the ER. This equilibrium may function to allow escape of wild-type subunits from aberrant retained subunits.
Zagouras
P
P
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510.
Ruusala
A
A
Rose
J K
JK
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001483:Base Sequence; D001692:Biological Transport; D020126:Brefeldin A; D002478:Cells, Cultured; D011232:Chemical Precipitation; D006224:Cricetinae; D003517:Cyclopentanes / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000378:metabolism*
D000998:Antiviral Agents; D003517:Cyclopentanes; C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; D020126:Brefeldin A