PathwayStep6597 PathwayStep6598 PathwayStep6594 PathwayStep6595 PathwayStep6596 Export of peptide loaded MHC class I complex to PM Egress of internalized antigen to the cytosol via sec61 Translocation of antigenic peptides back to phagosomes via TAP Proteasomal cleavage of substrate Peptide loading on MHC class I in phagosome ER-Phagosome pathway Authored: Garapati, P V, 2011-03-28 Edited: Garapati, P V, 2011-03-28 GENE ONTOLOGYGO:0002479 Pubmed12151002 Pubmed12669019 Pubmed14508489 Pubmed14508490 Pubmed14561893 Pubmed15728715 Pubmed15845646 Pubmed16213220 Pubmed17027300 Pubmed18006660 Pubmed18802471 Pubmed20171863 Reactome Database ID Release 431236974 Reactome, http://www.reactome.org ReactomeREACT_111178 Reviewed: Desjardins, M, English, L, 2011-05-13 The other TAP-dependent cross-presentation mechanism in phagocytes is the endoplasmic reticulum (ER)-phagosome model. Desjardins proposed that ER is recruited to the cell surface, where it fuses with the plasma membrane, underneath phagocytic cups, to supply membrane for the formation of nascent phagosomes (Gagnon et al. 2002). Three independent studies simultaneously showed that ER contributes to the vast majority of phagosome membrane (Guermonprez et al. 2003, Houde et al. 2003, Ackerman et al. 2003). The composition of early phagosome membrane contains ER-resident proteins, the components required for cross-presentation. This model is similar to the phagosome-to-cytosol model in that Ag is translocated to cytosol for proteasomal degradation, but differs in that antigenic peptides are translocated back into the phagosome (instead of ER) for peptide:MHC-I complexes. ER fusion with phagosome introduces molecules that are involved in Ag transport to cytosol (Sec61) and proteasome-generated peptides back into the phagosome (TAP) for loading onto MHC-I. <br>Through extensive biochemical assays, fluorescent imaging and electron microscopy-based experiments, most of the evidence in favor of ER-phagocytosis has been challenged (Touret et al. 2005a/b). Using quantitative proteomics Roger and Foster have shown that the percentage of PM and ER membranes on phagosomes 10 min after internalization was approximately 10% and 0.2% (Rogers et al. 2007). They concluded that ER contributes only a small part of phagosomal membranes.<br>Although the ER-phagosome pathway is controversial, the concept remains attractive as it explains how peptide-receptive MHC-I molecules could intersect with a relatively high concentration of exogenous antigens, presumably a crucial prerequisite for efficient cross-presentation (Basha et al. 2008).