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HHV-7 U21 exploits Golgi quality control carriers to reroute class I MHC molecules to lysosomes.


ABSTRACT: The human herpesvirus-7 (HHV-7) U21 glycoprotein binds to class I major histocompatibility complex (MHC) molecules in the endoplasmic reticulum (ER) and reroutes them to lysosomes. How this single viral glycoprotein efficiently redirects the U21/class I MHC complex to the lysosomal compartment is poorly understood. To investigate the trafficking of HHV-7 U21, we followed synchronous release of U21 from the ER as it traffics through the secretory system. Sorting of integral membrane proteins from the trans-Golgi network (TGN) has been shown to occur through tubular carriers that emanate from the TGN or through vesicular carriers that recruit GGA (Golgi-localized, ?-ear-containing, ARF-binding protein), clathrin adaptors, and clathrin. Here, we present evidence for the existence of a third type of Golgi-derived carrier that is vesicular, yet clathrin independent. This U21-containing carrier also carries a Golgi membrane protein engineered to form inducible oligomers. We propose that U21 employs the novel mechanism of forming oligomeric complexes with class I MHC molecules that result in sorting of the oligomeric U21/class I MHC complexes to Golgi--derived quality control carriers destined for lysosomes.

SUBMITTER: Dirck AT 

PROVIDER: S-EPMC7001482 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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HHV-7 U21 exploits Golgi quality control carriers to reroute class I MHC molecules to lysosomes.

Dirck Aaron T AT   Whyte Melissa L ML   Hudson Amy W AW  

Molecular biology of the cell 20191218 3


The human herpesvirus-7 (HHV-7) U21 glycoprotein binds to class I major histocompatibility complex (MHC) molecules in the endoplasmic reticulum (ER) and reroutes them to lysosomes. How this single viral glycoprotein efficiently redirects the U21/class I MHC complex to the lysosomal compartment is poorly understood. To investigate the trafficking of HHV-7 U21, we followed synchronous release of U21 from the ER as it traffics through the secretory system. Sorting of integral membrane proteins from  ...[more]

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