Abstract
Lipids are not encoded by a DNA template and therefore cannot be mutated, knocked out or knocked down. This by no means renders them impotent from a cell biological perspective. Here I propose a model for the involvement of lipid rearrangements in the execution of crucial steps in (glyco)protein quality control.
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References
Osborne, A. R., Rapoport, T. A. & van den Berg, B. Protein translocation by the Sec61/SecY channel. Annu. Rev. Cell Dev. Biol. 21, 529–550 (2005)
Meusser, B., Hirsch, C., Jarosch, E. & Sommer, T. ERAD: the long road to destruction. Nature Cell Biol. 7, 766–772 (2005)
Romisch, K. Endoplasmic reticulum-associated degradation. Annu. Rev. Cell Dev. Biol. 21, 435–456 (2005)
Tsai, B., Ye, Y. & Rapoport, T. A. Retro-translocation of proteins from the endoplasmic reticulum into the cytosol. Nature Rev. Mol. Cell Biol. 3, 246–255 (2002)
Ellgaard, L. & Helenius, A. Quality control in the endoplasmic reticulum. Nature Rev. Mol. Cell Biol. 4, 181–191 (2003)
Goldberg, A. L. Protein degradation and protection against misfolded or damaged proteins. Nature 426, 895–899 (2003)
Varshavsky, A. Regulated protein degradation. Trends Biochem. Sci. 30, 283–286 (2005)
Schekman, R. Cell biology: a channel for protein waste. Nature 429, 817–818 (2004)
Wiertz, E. J. et al. Sec61-mediated transfer of a membrane protein from the endoplasmic reticulum to the proteasome for destruction. Nature 384, 432–438 (1996)
Ye, Y., Shibata, Y., Yun, C., Ron, D. & Rapoport, T. A. A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol. Nature 429, 841–847 (2004)
Lilley, B. N. & Ploegh, H. L. A membrane protein required for dislocation of misfolded proteins from the ER. Nature 429, 834–840 (2004)
Pelkmans, L., Puntener, D. & Helenius, A. Local actin polymerization and dynamin recruitment in SV40-induced internalization of caveolae. Science 296, 535–539 (2002)
Lilley, B. N., Gilbert, J. M., Ploegh, H. L. & Benjamin, T. L. Murine polyomavirus requires the endoplasmic reticulum protein Derlin-2 to initiate infection. J. Virol. 80, 8739–8744 (2006)
Gilbert, J., Ou, W., Silver, J. & Benjamin, T. Downregulation of protein disulfide isomerase inhibits infection by the mouse polyomavirus. J. Virol. 80, 10868–10870 (2006)
Tauchi-Sato, K., Ozeki, S., Houjou, T., Taguchi, R. & Fujimoto, T. The surface of lipid droplets is a phospholipid monolayer with a unique Fatty Acid composition. J. Biol. Chem. 277, 44507–44512 (2002)
Martin, S. & Parton, R. G. Lipid droplets: a unified view of a dynamic organelle. Nature Rev. Mol. Cell Biol. 7, 373–378 (2006)
McManaman, J. L., Zabaronick, W., Schaack, J. & Orlicky, D. J. Lipid droplet targeting domains of adipophilin. J. Lipid Res. 44, 668–673 (2003)
Ostermeyer, A. G. et al. Accumulation of caveolin in the endoplasmic reticulum redirects the protein to lipid storage droplets. J. Cell Biol. 152, 1071–1078 (2001)
Umlauf, E. et al. Association of stomatin with lipid bodies. J. Biol. Chem. 279, 23699–23709 (2004)
Liu, P. et al. Chinese hamster ovary K2 cell lipid droplets appear to be metabolic organelles involved in membrane traffic. J. Biol. Chem. 279, 3787–3792 (2004)
Brasaemle, D. L., Dolios, G., Shapiro, L. & Wang, R. Proteomic analysis of proteins associated with lipid droplets of basal and lipolytically stimulated 3T3–L1 adipocytes. J. Biol. Chem. 279, 46835–46842 (2004)
Baumgart, T., Hess, S. T. & Webb, W. W. Imaging coexisting fluid domains in biomembrane models coupling curvature and line tension. Nature 425, 821–824 (2003)
van Meer, G. & Sprong, H. Membrane lipids and vesicular traffic. Curr. Opin. Cell Biol. 16, 373–378 (2004)
Pelkmans, L., Kartenbeck, J. & Helenius, A. Caveolar endocytosis of simian virus 40 reveals a new two-step vesicular-transport pathway to the ER. Nature Cell Biol. 3, 473–483 (2001)
Liao, S., Lin, J., Do, H. & Johnson, A. E. Both lumenal and cytosolic gating of the aqueous ER translocon pore are regulated from inside the ribosome during membrane protein integration. Cell 90, 31–41 (1997)
de Jong, A. S. et al. The coxsackievirus 2B protein increases efflux of ions from the endoplasmic reticulum and Golgi, thereby inhibiting protein trafficking through the Golgi. J. Biol. Chem. 281, 14144–14150 (2006)
van Kuppeveld, F. J. et al. Coxsackievirus protein 2B modifies endoplasmic reticulum membrane and plasma membrane permeability and facilitates virus release. EMBO J. 16, 3519–3532 (1997)
Wiertz, E. J. et al. The human cytomegalovirus US11 gene product dislocates MHC class I heavy chains from the endoplasmic reticulum to the cytosol. Cell 84, 769–779 (1996)
Blom, D., Hirsch, C., Stern, P., Tortorella, D. & Ploegh, H. L. A glycosylated type I membrane protein becomes cytosolic when peptide: N-glycanase is compromised. EMBO J. 23, 650–658 (2004)
Misaghi, S., Pacold, M. E., Blom, D., Ploegh, H. L. & Korbel, G. A. Using a small molecule inhibitor of peptide: N-glycanase to probe its role in glycoprotein turnover. Chem. Biol. 11, 1677–1687 (2004)
Daniels, R., Svedine, S. & Hebert, D. N. N-linked carbohydrates act as lumenal maturation and quality control protein tags. Cell Biochem. Biophys. 41, 113–138 (2004)
Rudd, P. M. et al. The effects of variable glycosylation on the functional activities of ribonuclease, plasminogen and tissue plasminogen activator. Biochim. Biophys. Acta 1248, 1–10 (1995)
Tirosh, B., Furman, M. H., Tortorella, D. & Ploegh, H. L. Protein unfolding is not a prerequisite for endoplasmic reticulum-to-cytosol dislocation. J. Biol. Chem. 278, 6664–6672 (2003)
Fiebiger, E., Story, C., Ploegh, H. L. & Tortorella, D. Visualization of the ER-to-cytosol dislocation reaction of a type I membrane protein. EMBO J. 21, 1041–1053 (2002)
Furman, M. H., Loureiro, J., Ploegh, H. L. & Tortorella, D. Ubiquitinylation of the cytosolic domain of a type I membrane protein is not required to initiate its dislocation from the endoplasmic reticulum. J. Biol. Chem. 278, 34804–34811 (2003)
Ohsaki, Y., Cheng, J., Fujita, A., Tokumoto, T. & Fujimoto, T. Cytoplasmic lipid droplets are sites of convergence of proteasomal and autophagic degradation of apolipoprotein B. Mol. Biol. Cell 17, 2674–2683 (2006)
Fujimoto, T. & Ohsaki, Y. Proteasomal and autophagic pathways converge on lipid droplets. Autophagy 2, 299–301 (2006)
Loureiro, J. & Ploegh, H. L. Antigen presentation and the ubiquitin-proteasome system in host-pathogen interactions. Adv. Immunol. 92, 225–305 (2006)
Heemels, M. T. & Ploegh, H. Generation, translocation, and presentation of MHC class I-restricted peptides. Annu. Rev. Biochem. 64, 463–491 (1995)
Cresswell, P. Assembly, transport, and function of MHC class II molecules. Annu. Rev. Immunol. 12, 259–293 (1994)
Cresswell, P., Ackerman, A. L., Giodini, A., Peaper, D. R. & Wearsch, P. A. Mechanisms of MHC class I-restricted antigen processing and cross-presentation. Immunol. Rev. 207, 145–157 (2005)
Ackerman, A. L. & Cresswell, P. Cellular mechanisms governing cross-presentation of exogenous antigens. Nature Immunol. 5, 678–684 (2004)
Guermonprez, P. et al. ER-phagosome fusion defines an MHC class I cross-presentation compartment in dendritic cells. Nature 425, 397–402 (2003)
Imai, J., Hasegawa, H., Maruya, M., Koyasu, S. & Yahara, I. Exogenous antigens are processed through the endoplasmic reticulum-associated degradation (ERAD) in cross-presentation by dendritic cells. Int. Immunol. 17, 45–53 (2005)
Ackerman, A. L., Giodini, A. & Cresswell, P. A role for the endoplasmic reticulum protein retrotranslocation machinery during crosspresentation by dendritic cells. Immunity 25, 607–617 (2006)
Acknowledgements
I thank E. Klemm, J. Loureiro and B. Mueller, as well as D. Hoekstra and G. van Meer, for discussions. I thank T. Di Cesare for the artwork.
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Ploegh, H. A lipid-based model for the creation of an escape hatch from the endoplasmic reticulum. Nature 448, 435–438 (2007). https://doi.org/10.1038/nature06004
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DOI: https://doi.org/10.1038/nature06004
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