Decreased endosomal delivery of major histocompatibility complex class II-invariant chain complexes in dynamin-deficient cells.
Major histocompatibility complex class II molecules are heterodimeric cell surface molecules which acquire antigenic peptides in the endosomal/lysosomal system. Invariant chain (Ii), a third chain which is associated with class II molecules intracellularly mediates the endosomal targeting, but it is debated whether class II molecules reach the endosomal system mainly from the trans-Golgi network or via the cell surface. Dynamin is a cytosolic GTPase which is necessary for the formation of clathrin-coated vesicles from the plasma membrane, but which is not required for vesicle formation from the trans-Golgi network. Here we have used HeLa cells expressing a dominant negative form of dynamin to show that inhibition of clathrin-mediated uptake from the plasma membrane leads to accumulation of transfected Ii-class II complexes at the cell surface, while delivery of such complexes to endosomes/lysosomes is decreased. Our data therefore suggest that in this experimental system the majority of Ii-class II complexes traverse the cell surface before they reach the endosomal system.
Wang
K
K
The R. W. Johnson Pharmaceutical Research Institute, San Diego, California 92121, USA.
Peterson
P A
PA
Karlsson
L
L
D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D002478:Cells, Cultured; D034281:Dynamins; D004591:Electrophoresis, Polyacrylamide Gel; D011992:Endosomes / Q000378:metabolism*; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000502:physiology*; D006056:Golgi Apparatus / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000378:metabolism; D006367:HeLa Cells; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D013499:Surface Properties; D014162:Transfection
D000944:Antigens, Differentiation, B-Lymphocyte; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D046911:Macromolecular Substances; C045084:invariant chain; D020558:GTP Phosphohydrolases; D034281:Dynamins