title: Adaptor protein complexes AP-1 and AP-3 are required by the HHV-7 Immunoevasin U21 for rerouting of class I MHC molecules to the lysosomal compartment.
abstract: The human herpesvirus-7 (HHV-7) U21 gene product binds to class I major histocompatibility complex (MHC) molecules and reroutes them to a lysosomal compartment. Trafficking of integral membrane proteins to lysosomes is mediated through cytoplasmic sorting signals that recruit heterotetrameric clathrin adaptor protein (AP) complexes, which in turn mediate protein sorting in post-Golgi vesicular transport. Since U21 can mediate rerouting of class I molecules to lysosomes even when lacking its cytoplasmic tail, we hypothesize the existence of a cellular protein that contains the lysosomal sorting information required to escort class I molecules to the lysosomal compartment. If such a protein exists, we expect that it might recruit clathrin adaptor protein complexes as a means of lysosomal sorting. Here we describe experiments demonstrating that the μ adaptins from AP-1 and AP-3 are involved in U21-mediated trafficking of class I molecules to lysosomes. These experiments support the idea that a cellular protein(s) is necessary for U21-mediated lysosomal sorting of class I molecules. We also examine the impact of transient versus chronic knockdown of these adaptor protein complexes, and show that the few remaining μ subunits in the cells are eventually able to reroute class I molecules to lysosomes.
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Kimpler
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Glosson
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Deanna
authors.initials: D
authors.lastname: Downs
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Patrick
authors.initials: P
authors.lastname: Gonyo
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: May
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Amy W
authors.initials: AW
authors.lastname: Hudson
mesh_terms: D033961:Adaptor Protein Complex 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D033962:Adaptor Protein Complex 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D033963:Adaptor Protein Complex 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D033983:Adaptor Protein Complex mu Subunits / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D057809:HEK293 Cells; D016199:Herpesvirus 7, Human / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D018146:Muromegalovirus / Q000378:metabolism; D021381:Protein Transport; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D033961:Adaptor Protein Complex 1; D033962:Adaptor Protein Complex 2; D033963:Adaptor Protein Complex 3; D033983:Adaptor Protein Complex mu Subunits; D002352:Carrier Proteins; D015395:Histocompatibility Antigens Class I; D034741:RNA, Small Interfering; C488324:U21 glycoprotein, human herpesvirus 7; D014759:Viral Envelope Proteins; D014764:Viral Proteins