A lipid associated with the antiphospholipid syndrome regulates endosome structure and function
Abstract
Little is known about the structure and function of membrane domains in the vacuolar apparatus of animal cells. A unique feature of late endosomes, which are part of the pathway that leads to lysosomes, is that they contain a complex system of poorly characterized internal membranes in their lumen. These endosomes are therefore known as multivesicular or multilamellar organelles. Some proteins distribute preferentially within these internal membranes, whereas others are exclusively localized to the organelle's limiting membrane. The composition and function of this membrane system are poorly understood. Here we show that these internal membranes contain large amounts of a unique lipid, and thus form specialized domains within endosomes. These specialized domains are involved in sorting the multifunctional receptor for insulin-like growth factor 2 and ligands bearing mannose-6-phosphate, in particular lysosomal enzymes. We also show that this unique lipid is a specific antigen for human antibodies associated with the antiphospholipid syndrome. These antibodies may act intracellularly by altering the protein-sorting functions of endosomes.
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Lyso-biphosphatidic acids are key lipids of late endosomes/phagosomes and terminal phospholipid degradation products.
“Lyso-biphosphatidic acids (LBPA) are key lipids of late endosomes/phagosomes and terminal phospholipid degradation products (44).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [44]
Cites
ENDOCYTOSIS AND MOLECULAR SORTING
Mellman, I. (1996) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.12.1.575 · Cited by 1,521 · see citing works
Localization of low molecular weight GTP binding proteins to exocytic and endocytic compartments
Chavrier, P., Parton, R. G., Hauri, H. P., Simons, K., & Zerial, M. (1990) · Cell · doi:10.1016/0092-8674(90)90369-p · Cited by 1,166 · see citing works
Self-citationrab5 controls early endosome fusion in vitro
Gorvel, J., Chavrier, P., Zerial, M., & Gruenberg, J. E. (1991) · Cell · doi:10.1016/0092-8674(91)90316-q · Cited by 1,094 · see citing works
Self-citationSTRUCTURE AND FUNCTION OF THE MANNOSE 6-PHOSPHATE/INSULINLIKE GROWTH FACTOR II RECEPTORS
Kornfeld, S. A. (1992) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.61.070192.001515 · Cited by 1,081 · see citing works
The mannose 6-phosphate receptor and the biogenesis of lysosomes
Griffiths, G. W., Hoflack, B., Simons, K., Mellman, I., & Kornfeld, S. A. (1988) · Cell · doi:10.1016/s0092-8674(88)80026-6 · Cited by 856 · see citing works
Membrane transport in the endocytic pathway
Gruenberg, J. E., & Maxfield, F. R. (1995) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(95)80013-1 · Cited by 645 · see citing works
Self-citationGruenberg, J. E., Griffiths, G. W., & Howell, K. E. (1989) · The Journal of Cell Biology · doi:10.1083/jcb.108.4.1301 · Cited by 586 · see citing works
Self-citationImmunology and clinical importance of antiphospholipid antibodies
McNeil, H. P., Chesterman, C. N., & Krilis, S. A. (1991) · Advances in immunology · doi:10.1016/s0065-2776(08)60777-4 · Cited by 481 · see citing works
Regulation of embryonic growth and lysosomal targeting by the imprintedIgf2/Mpr gene
Wang, Z., Fung, M. R., Barlow, D. P., & Wagner, E. F. (1994) · Nature · doi:10.1038/372464a0 · Cited by 472 · see citing works
On the preparation of cryosections for immunocytochemistry
Griffiths, G. W., McDowall, A. W., Back, R., & Dubochet, J. (1984) · Journal of Ultrastructure Research · doi:10.1016/s0022-5320(84)80024-6 · Cited by 461 · see citing works
Aniento, F. (1993) · The Journal of Cell Biology · doi:10.1083/jcb.123.6.1373 · Cited by 404 · see citing works
An NSF-like ATPase, p97, and NSF mediate cisternal regrowth from mitotic golgi fragments
Rabouille, C., Levine, T. P., Peters, J., & Warren, G. (1995) · Cell · doi:10.1016/0092-8674(95)90270-8 · Cited by 361 · see citing works
Hörkkö, S., Miller, E. R., Dudl, E. P., Reaven, P. D., Curtiss, L. K., Zvaifler, N., Terkeltaub, R. A., Pierangeli, S. S., Branch, D. W., Palinski, W., et al. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118854 · Cited by 348 · see citing works
The formation of golgi stacks from vesiculated golgi membranes requires two distinct fusion events
Acharya, U. R., Jacobs, R., Peters, J., Watson, N., Farquhar, M. G., & Malhotra, V. (1995) · Cell · doi:10.1016/0092-8674(95)90269-4 · Cited by 208 · see citing works
Functional Dissection of COP-I Subunits in the Biogenesis of Multivesicular Endosomes
Gu, F., Aniento, F., Parton, R. G., et al. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.139.5.1183 · Cited by 169 · see citing works
Self-citationReaves, B. J., Horn, M., & Banting, G. S. (1993) · Molecular Biology of the Cell · doi:10.1091/mbc.4.1.93 · Cited by 148 · see citing works
Coatomer (COPI)-coated vesicles: role in intracellular transport and protein sorting
Cosson, P., & Letourneur, F. (1997) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(97)80023-3 · Cited by 142 · see citing works
Enrichment of Bis-(monoacylglyceryl) Phosphate in Lysosomes from Rat Liver
Wherrett, J. R., & Huterer, S. J. (1972) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)45047-3 · Cited by 136 · see citing works
Novel stereoconfiguration in lyso-bis-phosphatidic acid of cultured BHK-cells
Brotherus, J. R., Renkonen, O., Herrmann, J., et al. (1974) · Chemistry and Physics of Lipids · doi:10.1016/0009-3084(74)90034-6 · Cited by 120 · see citing works
Volpert, O. V., Jackson, D., BOUCK, N. P., et al. (1996) · Endocrinology · doi:10.1210/endo.137.9.8756559 · Cited by 103 · see citing works
Ludwig, T. E. (1995) · Trends in Cell Biology · doi:10.1016/s0962-8924(00)89000-5 · Cited by 79 · see citing works
Groskopf, J. C., Syu, L.-J., Saltiel, A. R., & Linzer, D. I. H. (1997) · Endocrinology · doi:10.1210/endo.138.7.5276 · Cited by 77 · see citing works
Management of Thrombosis in the Antiphospholipid Syndrome
Khamashta, M. A. (1996) · Lupus · doi:10.1177/096120339600500527 · Cited by 69 · see citing works
The antiphospholipid/cofactor syndromes.
Alarcón-Segovia, D., & Cabral, A. R. (1996) · PubMed · Cited by 61 · see citing works
Umeda, M., Igarashi, K., Nam, K., et al. (1989) · The Journal of Immunology · doi:10.4049/jimmunol.143.7.2273 · Cited by 45 · see citing works
Glycerophospho-(N-acyl)-ethanolamine lipids in degenerating bhk cells
Somerharju, P. J., & Renkonen, O. (1979) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(79)90175-9 · Cited by 38 · see citing works
Gharavi, A. E., & Wilson, W. (1996) · Lupus · doi:10.1177/096120339600500501 · Cited by 37 · see citing works
(2011) · SpringerReference · doi:10.1007/springerreference_37528 · Cited by 32 · see citing works
The stereoconfiguration of newly formed molecules of BIS(monoacylglycero)phosphate in BHK cells
Joutti, A. (1979) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(79)90125-5 · Cited by 32 · see citing works
Ludwig, T. E., Borgne, R. L., & Hoflack, B. (1995) · Trends in Cell Biology · doi:10.1016/0962-8924(95)80012-6 · Cited by 27 · see citing works
Reber, G., Tremblet, C., Bernard, C., Mermillod, B., & de Moerloose, P. (1990) · Thrombosis Research · doi:10.1016/0049-3848(90)90321-3 · Cited by 14 · see citing works
Karasawa, K., Satoh, N., Hongo, T., et al. (1991) · Lipids · doi:10.1007/bf02536514 · Cited by 5 · see citing works
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Macrophage defense mechanisms against intracellular bacteria
Weiss, G., & Schaible, U. E. (2015) · Immunological Reviews · doi:10.1111/imr.12266 · Cited by 989 · see citing works
Zhong, Y., Wang, Q. J., Li, X., Yan, Y., Backer, J. M., Chait, B. T., Heintz, N., & Yue, Z. (2009) · Nature Cell Biology · doi:10.1038/ncb1854 · Cited by 1,005 · see citing works
Antimicrobial mechanisms of phagocytes and bacterial evasion strategies
Flannagan, R. S., Cosío, G., & Grinstein, S. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2128 · Cited by 947 · see citing works
The lysosome: from waste bag to potential therapeutic target
Appelqvist, H., Wäster, P., Kågedal, K., & Öllinger, K. (2013) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjt022 · Cited by 772 · see citing works
Biogenesis and Function of Multivesicular Bodies
Piper, R. C., & Katzmann, D. J. (2007) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.23.090506.123319 · Cited by 771 · see citing works
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Matsuo, H., Chevallier, J., Mayran, N., Le Blanc, I., Ferguson, C., Fauré, J., Blanc, N. S., Matile, S., Dubochet, J., Sadoul, R., et al. (2004) · Science · doi:10.1126/science.1092425 · Cited by 705 · see citing works
Self-citationHsp70 stabilizes lysosomes and reverts Niemann–Pick disease-associated lysosomal pathology
Kirkegaard, T., Roth, A. G., Petersen, N. H. T., Mahalka, A. K., Olsen, O. D., Moilanen, I., Zylicz, A., Knudsen, J., Sandhoff, K., Arenz, C., et al. (2010) · Nature · doi:10.1038/nature08710 · Cited by 519 · see citing works
Schneiter, R., Brügger, B., Sandhoff, R., Zellnig, G., Leber, A., Lampl, M., Athenstaedt, K., Hrastnik, C., Eder, S., Daum, G., et al. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.146.4.741 · Cited by 493 · see citing works
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Takahashi, R. H., Almeida, C. G., Kearney, P. F., Yu, F., Lin, M. T., Milner, T. A., & Gouras, G. K. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.5167-03.2004 · Cited by 445 · see citing works
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Larios, J., Mercier, V., Roux, A., & Gruenberg, J. (2020) · Journal of Cell Biology · doi:10.1083/jcb.201904113 · Cited by 422 · see citing works
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Verkhratsky, A., Matteoli, M., Parpura, V., Mothet, J., & Zorec, R. (2016) · The EMBO Journal · doi:10.15252/embj.201592705 · Cited by 397 · see citing works
ALIX and the multivesicular endosome: ALIX in Wonderland
Bissig, C., & Gruenberg, J. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2013.10.009 · Cited by 323 · see citing works
Self-citationExtracellular vesicles: lipids as key components of their biogenesis and functions
Record, M., Silvente-Poirot, S., Poirot, M., & Wakelam, M. O. (2018) · Journal of Lipid Research · doi:10.1194/jlr.e086173 · Cited by 328 · see citing works
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Mutka, A.-L., Lusa, S., Linder, M. D., Jokitalo, E., Kopra, O., Jauhiainen, M., & Ikonen, E. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m405345200 · Cited by 56 · see citing works
Dinkel, L., Hummel, S., Zenatti, V., Malara, M., Tillmann, Y., Colombo, A., Monasor, L. S., Suh, J. H., Logan, T., Roth, S., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adl4616 · Cited by 22 · see citing works
- Authors
- Kobayashi, T., Stang, E., Fang, K. S., de Moerloose, P., Parton, R. G., & Gruenberg, J.
- Affiliations
- University of Geneva (CH)
- The University of Queensland (AU)
- Corresponding author
- Gruenberg, Jean
- Venue
- Nature
- Published
- 1998-03
- Volume
- 392
- Issue
- 6672
- Pages
- 193-197
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1495951828
- Cited by
- 787
- References
- 32
- Citations by year
- 2026: 15 · 2025: 15 · 2024: 17 · 2023: 24 · 2022: 20 · 2021: 21 · 2020: 30 · 2019: 15 · 2018: 24 · 2017: 20 · 2016: 23 · 2015: 16 · 2014: 27 · 2013: 22 · 2012: 19
- FWCI
- 17.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- antiphospholipid syndrome, lipid rafts, multivesicular endosomes, late endosomes, mannose 6-phosphate receptor, IGF2R, lysosomal enzyme sorting, lysosomal enzymes, protein sorting
- MeSH terms
- Animals, Antibodies, Monoclonal, Biological Transport, Cell Line, Cricetinae, Humans, Intracellular Membranes, Lipids, Lysophospholipids, Membrane Glycoproteins, Endosomes, Antigens, CD, Antiphospholipid Syndrome, Receptor, IGF Type 2, Monoglycerides, Lysosomal Membrane Proteins
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