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ER-Phagosome pathway (R-HSA-1236974)

Species Homo sapiens


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.
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.
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).

Locations in the PathwayBrowser
Additional Information
GO Biological Process antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent (0002479)
Literature References
pubMedId Title Journal Year
14561893 Early phagosomes in dendritic cells form a cellular compartment sufficient for cross presentation of exogenous antigens Proc Natl Acad Sci U S A 2003
14508489 ER-phagosome fusion defines an MHC class I cross-presentation compartment in dendritic cells Nature 2003
14508490 Phagosomes are competent organelles for antigen cross-presentation Nature 2003
12151002 Endoplasmic reticulum-mediated phagocytosis is a mechanism of entry into macrophages Cell 2002
20171863 Intracellular mechanisms of antigen cross presentation in dendritic cells Curr Opin Immunol 2010
18006660 The dynamic phagosomal proteome and the contribution of the endoplasmic reticulum Proc Natl Acad Sci U S A 2007
15728715 The nature of the phagosomal membrane: endoplasmic reticulum versus plasmalemma J Leukoc Biol 2005
16213220 Quantitative and dynamic assessment of the contribution of the ER to phagosome formation Cell 2005
17027300 A role for the endoplasmic reticulum protein retrotranslocation machinery during crosspresentation by dendritic cells Immunity 2006
15845646 ER-mediated phagocytosis: myth or reality? J Leukoc Biol 2005
Inferred Entries
Orthologous events
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