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. PLoS One 2014;9(6):e99139
Date
06/06/2014Pubmed ID
24901711Pubmed Central ID
PMC4047081DOI
10.1371/journal.pone.0099139Scopus ID
2-s2.0-84902477273 (requires institutional sign-in at Scopus site) 4 CitationsAbstract
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.
Author List
Kimpler LA, Glosson NL, Downs D, Gonyo P, May NA, Hudson AWAuthor
Amy W. Hudson PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adaptor Protein Complex 1Adaptor Protein Complex 2
Adaptor Protein Complex 3
Adaptor Protein Complex mu Subunits
Carrier Proteins
Cell Line
Cell Membrane
HEK293 Cells
Herpesvirus 7, Human
Histocompatibility Antigens Class I
Humans
Lysosomes
Muromegalovirus
Protein Transport
RNA Interference
RNA, Small Interfering
Viral Envelope Proteins
Viral Proteins
