The major substrates for TAP in vivo are derived from newly synthesized proteins.
The transporter associated with antigen processing (TAP) is a member of the family of ABC transporters that translocate a large variety of substrates across membranes. TAP transports peptides from the cytosol into the endoplasmic reticulum for binding to MHC class I molecules and for subsequent presentation to the immune system. Here we follow the lateral mobility of TAP in living cells. TAP's mobility increases when it is inactive and decreases when it translocates peptides. Because TAP activity is dependent on substrate, the mobility of TAP is used to monitor the intracellular peptide content in vivo. Comparison of the diffusion rates in peptide-free and peptide-saturated cells indicates that normally about one-third of all TAP molecules actively translocate peptides. However, during an acute influenza infection TAP becomes fully employed owing to the production and degradation of viral proteins. Furthermore, TAP activity depends on continuing protein translation. This implies that MHC class I molecules mainly sample peptides that originate from newly synthesized proteins, to ensure rapid presentation to the immune system.
Reits
E A
EA
Division of Tumor Biology, The Netherlands Cancer Institute, Amsterdam.
Vos
J C
JC
Grommé
M
M
Neefjes
J
J
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D001692:Biological Transport; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D049452:Green Fluorescent Proteins; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D008164:Luminescent Proteins; D011487:Protein Conformation; D011506:Proteins / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000378:metabolism
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015853:Cysteine Proteinase Inhibitors; D015789:HLA-A2 Antigen; D008164:Luminescent Proteins; D011506:Proteins; C073119:TAP1 protein, human; D014764:Viral Proteins; C067713:lactacystin; D049452:Green Fluorescent Proteins; D000111:Acetylcysteine