Reactome | ER-Phagosome pathway

ER-Phagosome pathway

Stable Identifier

R-HSA-1236974

DOI

10.3180/R-HSA-1236974.2

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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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.
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).

Literature References

PubMed ID	Title	Journal	Year
15728715	The nature of the phagosomal membrane: endoplasmic reticulum versus plasmalemma Paroutis, P, Grinstein, S, Touret, N	J Leukoc Biol	2005
20171863	Intracellular mechanisms of antigen cross presentation in dendritic cells Savina, A, Amigorena, S	Curr Opin Immunol	2010
22915823	Proteomic characterization of phagosomal membrane microdomains during phagolysosome biogenesis and evolution Barreiro, L, Carruthers, NJ, LaBoissière, S, Goyette, G, Dermine, JF, Desjardins, M, Michnick, SW, Landry, CR, Boulais, J, Lajoie, G, Jutras, I, Thibault, P, Duclos, S	Mol. Cell Proteomics	2012
14508490	Phagosomes are competent organelles for antigen cross-presentation Houde, M, Brunet, S, Laplante, A, Goyette, G, Bertholet, S, Desjardins, M, Sacks, D, Gagnon, E, Thibault, P, Princiotta, MF	Nature	2003
15845646	ER-mediated phagocytosis: myth or reality? Bergeron, JJ, Desjardins, M, Gagnon, E	J Leukoc Biol	2005
18006660	The dynamic phagosomal proteome and the contribution of the endoplasmic reticulum Foster, LJ, Rogers, LD	Proc Natl Acad Sci U S A	2007
17027300	A role for the endoplasmic reticulum protein retrotranslocation machinery during crosspresentation by dendritic cells Ackerman, AL, Giodini, A, Cresswell, P	Immunity	2006
16213220	Quantitative and dynamic assessment of the contribution of the ER to phagosome formation Paroutis, P, Harrison, RE, van der Wel, N, Mellman, I, Grinstein, S, Chow, A, de Chastellier, C, Touret, N, Houben, D, Pypaert, M, Moore, HP, Trombetta, S, Shaw, J, Jiang, A, Yip, C, Peters, PJ, Terebiznik, M	Cell	2005
14508489	ER-phagosome fusion defines an MHC class I cross-presentation compartment in dendritic cells Guermonprez, P, Van Endert, P, Davoust, J, Amigorena, S, Kleijmeer, M, Saveanu, L	Nature	2003
12151002	Endoplasmic reticulum-mediated phagocytosis is a mechanism of entry into macrophages Paiement, J, Steele-Mortimer, O, Cameron, PH, Bergeron, JJ, Duclos, S, Desjardins, M, Gagnon, E, Chevet, E, Rondeau, C	Cell	2002
14561893	Early phagosomes in dendritic cells form a cellular compartment sufficient for cross presentation of exogenous antigens Ackerman, AL, Kyritsis, C, Cresswell, P, Tampé, R	Proc Natl Acad Sci U S A	2003