ER-Phagosome pathway

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Homo sapiens
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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
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