title: Intracellular transport of MHC class II and associated invariant chain in antigen presenting cells from AP-3-deficient mocha mice.
abstract: MHC class II-restricted antigen presentation requires trafficking of newly synthesized class II-invariant chain complexes from the trans-Golgi network to endosomal, peptide-loading compartments. This transport is mediated by dileucine-like motifs within the cytosolic tail of the invariant chain. Although these signals have been well characterized, the cytosolic proteins that interact with these dileucine signals and mediate Golgi sorting and endosomal transport have not been identified. Recently, an adaptor complex, AP-3, has been identified that interacts with dileucine motifs and mediates endosomal/lysosomal transport in yeast, Drosophila, and mammals. In this report, we have assessed class II-invariant chain trafficking in a strain of mice (mocha) which lacks expression of AP-3. Our studies demonstrate that the lack of AP-3 does not affect the kinetics of invariant chain degradation, the route of class II-invariant chain transport, or the rate and extent of class II-peptide binding as assessed by the generation of SDS-stable dimers. The possible role of other known or unknown adaptor complexes in class II-invariant chain transport is discussed.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Sevilla
authors.forename: S S
authors.initials: SS
authors.lastname: Richter
authors.forename: J
authors.initials: J
authors.lastname: Miller
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D020816:Amino Acid Motifs; D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry / Q000378:metabolism*; D001402:B-Lymphocytes / Q000201:enzymology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002451:Cell Compartmentation; D011992:Endosomes / Q000201:enzymology / Q000378:metabolism; D005838:Genotype; D006056:Golgi Apparatus / Q000378:metabolism; D006200:Hair Color / Q000235:genetics; D022861:Hermanski-Pudlak Syndrome / Q000145:classification / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D017496:Hypopigmentation / Q000235:genetics; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000201:enzymology; D046911:Macromolecular Substances; D008264:Macrophages / Q000201:enzymology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008818:Mice, Neurologic Mutants; D034041:Monomeric Clathrin Assembly Proteins; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D010981:Platelet Storage Pool Deficiency / Q000235:genetics; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D060149:Tetraspanin 30; D021601:trans-Golgi Network / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D002352:Carrier Proteins; C554587:Cd63 protein, mouse; D000949:Histocompatibility Antigens Class II; D051907:Lysosomal Membrane Proteins; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D034041:Monomeric Clathrin Assembly Proteins; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; C439023:clathrin assembly protein AP180; C045084:invariant chain