Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 280, Issue 20, Pages 19656-19664Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M501357200
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Newly synthesized MHC II alpha- and beta-chains associated with the invariant chain chaperone (Ii) enter the endocytic pathway for Ii degradation and loading with peptides before transport to the cell surface. It is unclear how alpha beta Ii complexes are sorted from the Golgi apparatus and directed to endosomes. However, indirect evidence tends to support direct transport involving the AP1 clathrin adaptor complex. Surprisingly, we show here that knocking down the production of AP1 by RNA interference did not affect the trafficking of alpha beta Ii complexes. In contrast, AP2 depletion led to a large increase in surface levels of alpha beta Ii complexes, inhibited their rapid internalization, and strongly delayed the appearance of mature MHC II in intracellular compartments. Thus, in the cell systems studied here, rapid internalization of alpha beta Ii complexes via an AP2-dependent pathway represents a key step for MHC II delivery to endosomes and lysosomes.
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