Chaperone-mediated cross-priming: a hitchhiker's guide to vesicle transport (review).
The resident endoplasmic reticulum (ER) chaperone proteins GRP94 (gp96) and calreticulin can activate the immune system to slow or stop the progression of tumors by escorting tumor-derived peptides into the endogenous antigen presentation pathway of antigen presenting cells (APC). Although the phenomenology of cross-priming is well worked out, the mechanism(s) remains unclear. Continuing insights into cellular protein trafficking pathways suggest several means by which chaperones could travel from the extracellular space into the endosome, lysosome or ER of APC. In particular, proteins that cycle between two or more compartments and those that undergo and mediate retrograde flow offer models of how exogenous chaperones might travel in the APC. New insights into how non-chaperone proteins access the APC antigen presentation pathway also suggest several ways this process could occur.
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
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D000818:Animals; D001692:Biological Transport; D002135:Calcium-Binding Proteins / Q000502:physiology; D037282:Calreticulin; D004705:Endocytosis / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D011992:Endosomes / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology; D018832:Molecular Chaperones / Q000502:physiology*; D012261:Ribonucleoproteins / Q000502:physiology
D002135:Calcium-Binding Proteins; D037282:Calreticulin; D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D012261:Ribonucleoproteins; C018551:glucose-regulated proteins