title: Early endosomal rerouting of major histocompatibility class I conformers.
abstract: Major histocompatibility class I (MHC-I) molecules are present at the cell surface both as fully conformed trimolecular complexes composed of heavy chain (HC), beta-2-microglobulin (β2m) and peptide, and various open forms, devoid of peptide and/or β2m (open MHC-I conformers). Fully conformed MHC-I complexes and open MHC-I conformers can be distinguished by well characterized monoclonal antibody reagents that recognize their conformational difference in the extracellular domain. In the present study, we used these tools in order to test whether conformational difference in the extracellular domain determines endocytic and endosomal route of plasma membrane (PM) proteins. We analyzed PM localization, internalization, endosomal trafficking, and recycling of human and murine MHC-I proteins on various cell lines. We have shown that fully conformed MHC-I and open MHC-I conformers segregate at the PM and during endosomal trafficking resulting in the exclusion of open MHC-I conformers from the recycling route. This segregation is associated with their partitioning into the membranes of different compositions. As a result, the open MHC-I conformers internalized with higher rate than fully conformed counterparts. Thus, our data suggest the existence of conformation-based protein sorting mechanism in the endosomal system.
authors.affiliation: Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Gordana Blagojević
authors.initials: GB
authors.lastname: Zagorac
authors.forename: Hana
authors.initials: H
authors.lastname: Mahmutefendić
authors.forename: Maja Ilić
authors.initials: MI
authors.lastname: Tomaš
authors.forename: Natalia
authors.initials: N
authors.lastname: Kučić
authors.forename: Philippe
authors.initials: P
authors.lastname: Le Bouteiller
authors.forename: Pero
authors.initials: P
authors.lastname: Lučin
mesh_terms: D000818:Animals; D041702:BALB 3T3 Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D022163:Clathrin-Coated Vesicles / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000378:metabolism*; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D021381:Protein Transport
chemical_list: D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins