A ‘torn bag mechanism’ of small extracellular vesicle release via limiting membrane rupture of en bloc released amphisomes (amphiectosomes)
Recent studies showed an unexpected complexity of extracellular vesicle (EV) biogenesis pathways. We previously found evidence that human colorectal cancer cells in vivo release large multivesicular body-like structures en bloc. Here, we tested whether this large EV type is unique to colorectal canc...
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eLife Sciences Publications Ltd
2025-02-01
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| Online Access: | https://elifesciences.org/articles/95828 |
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| author | Tamás Visnovitz Dorina Lenzinger Anna Koncz Péter M Vizi Tünde Bárkai Krisztina V Vukman Alicia Galinsoga Krisztina Németh Kelsey Fletcher Zsolt I Komlósi Csaba Cserép Ádám Dénes Péter Lőrincz Gábor Valcz Edit I Buzas |
| author_facet | Tamás Visnovitz Dorina Lenzinger Anna Koncz Péter M Vizi Tünde Bárkai Krisztina V Vukman Alicia Galinsoga Krisztina Németh Kelsey Fletcher Zsolt I Komlósi Csaba Cserép Ádám Dénes Péter Lőrincz Gábor Valcz Edit I Buzas |
| author_sort | Tamás Visnovitz |
| collection | DOAJ |
| description | Recent studies showed an unexpected complexity of extracellular vesicle (EV) biogenesis pathways. We previously found evidence that human colorectal cancer cells in vivo release large multivesicular body-like structures en bloc. Here, we tested whether this large EV type is unique to colorectal cancer cells. We found that all cell types we studied (including different cell lines and cells in their original tissue environment) released multivesicular large EVs (MV-lEVs). We also demonstrated that upon spontaneous rupture of the limiting membrane of the MV-lEVs, their intraluminal vesicles (ILVs) escaped to the extracellular environment by a ‘torn bag mechanism’. We proved that the MV-lEVs were released by ectocytosis of amphisomes (hence, we termed them amphiectosomes). Both ILVs of amphiectosomes and small EVs separated from conditioned media were either exclusively CD63 or LC3B positive. According to our model, upon fusion of multivesicular bodies with autophagosomes, fragments of the autophagosomal inner membrane curl up to form LC3B positive ILVs of amphisomes, while CD63 positive small EVs are of multivesicular body origin. Our data suggest a novel common release mechanism for small EVs, distinct from the exocytosis of multivesicular bodies or amphisomes, as well as the small ectosome release pathway. |
| format | Article |
| id | doaj-art-030a17c96ac64e008f46481044198cd5 |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-030a17c96ac64e008f46481044198cd52025-02-07T14:42:43ZengeLife Sciences Publications LtdeLife2050-084X2025-02-011310.7554/eLife.95828A ‘torn bag mechanism’ of small extracellular vesicle release via limiting membrane rupture of en bloc released amphisomes (amphiectosomes)Tamás Visnovitz0https://orcid.org/0000-0002-7962-5083Dorina Lenzinger1https://orcid.org/0000-0003-0270-7985Anna Koncz2Péter M Vizi3Tünde Bárkai4Krisztina V Vukman5Alicia Galinsoga6Krisztina Németh7Kelsey Fletcher8Zsolt I Komlósi9Csaba Cserép10Ádám Dénes11Péter Lőrincz12https://orcid.org/0000-0001-7374-667XGábor Valcz13Edit I Buzas14https://orcid.org/0000-0002-3744-206XSemmelweis University, Department of Genetics, Cell- and Immunobiology, Budapest, Hungary; ELTE Eötvös Loránd University, Department of Plant Physiology and Molecular Plant Biology, Budapest, HungarySemmelweis University, Department of Genetics, Cell- and Immunobiology, Budapest, HungarySemmelweis University, Department of Genetics, Cell- and Immunobiology, Budapest, Hungary; HUN-REN-SU Translational Extracellular Vesicle Research Group, Budapest, HungarySemmelweis University, Department of Genetics, Cell- and Immunobiology, Budapest, HungarySemmelweis University, Department of Genetics, Cell- and Immunobiology, Budapest, HungarySemmelweis University, Department of Genetics, Cell- and Immunobiology, Budapest, HungarySemmelweis University, Department of Genetics, Cell- and Immunobiology, Budapest, HungarySemmelweis University, Department of Genetics, Cell- and Immunobiology, Budapest, Hungary; HUN-REN-SU Translational Extracellular Vesicle Research Group, Budapest, HungarySemmelweis University, Department of Genetics, Cell- and Immunobiology, Budapest, HungarySemmelweis University, Department of Genetics, Cell- and Immunobiology, Budapest, HungaryLaboratory of Neuroimmunology, HUN-REN Institute of Experimental Medicine, Budapest, HungaryLaboratory of Neuroimmunology, HUN-REN Institute of Experimental Medicine, Budapest, HungaryELTE Eötvös Loránd University, Department of Anatomy, Cell and Developmental Biology, Budapest, HungarySemmelweis University, Department of Genetics, Cell- and Immunobiology, Budapest, Hungary; HUN-REN-SU Translational Extracellular Vesicle Research Group, Budapest, Hungary; Department of Image Analysis, 3DHISTECH Ltd, Budapest, HungarySemmelweis University, Department of Genetics, Cell- and Immunobiology, Budapest, Hungary; HUN-REN-SU Translational Extracellular Vesicle Research Group, Budapest, Hungary; HCEMM-SU Extracellular Vesicle Research Group, Hungary, Budapest, HungaryRecent studies showed an unexpected complexity of extracellular vesicle (EV) biogenesis pathways. We previously found evidence that human colorectal cancer cells in vivo release large multivesicular body-like structures en bloc. Here, we tested whether this large EV type is unique to colorectal cancer cells. We found that all cell types we studied (including different cell lines and cells in their original tissue environment) released multivesicular large EVs (MV-lEVs). We also demonstrated that upon spontaneous rupture of the limiting membrane of the MV-lEVs, their intraluminal vesicles (ILVs) escaped to the extracellular environment by a ‘torn bag mechanism’. We proved that the MV-lEVs were released by ectocytosis of amphisomes (hence, we termed them amphiectosomes). Both ILVs of amphiectosomes and small EVs separated from conditioned media were either exclusively CD63 or LC3B positive. According to our model, upon fusion of multivesicular bodies with autophagosomes, fragments of the autophagosomal inner membrane curl up to form LC3B positive ILVs of amphisomes, while CD63 positive small EVs are of multivesicular body origin. Our data suggest a novel common release mechanism for small EVs, distinct from the exocytosis of multivesicular bodies or amphisomes, as well as the small ectosome release pathway.https://elifesciences.org/articles/95828exosomesamphisomeextracellular vesiclesautophagysecretionbiogenesis |
| spellingShingle | Tamás Visnovitz Dorina Lenzinger Anna Koncz Péter M Vizi Tünde Bárkai Krisztina V Vukman Alicia Galinsoga Krisztina Németh Kelsey Fletcher Zsolt I Komlósi Csaba Cserép Ádám Dénes Péter Lőrincz Gábor Valcz Edit I Buzas A ‘torn bag mechanism’ of small extracellular vesicle release via limiting membrane rupture of en bloc released amphisomes (amphiectosomes) eLife exosomes amphisome extracellular vesicles autophagy secretion biogenesis |
| title | A ‘torn bag mechanism’ of small extracellular vesicle release via limiting membrane rupture of en bloc released amphisomes (amphiectosomes) |
| title_full | A ‘torn bag mechanism’ of small extracellular vesicle release via limiting membrane rupture of en bloc released amphisomes (amphiectosomes) |
| title_fullStr | A ‘torn bag mechanism’ of small extracellular vesicle release via limiting membrane rupture of en bloc released amphisomes (amphiectosomes) |
| title_full_unstemmed | A ‘torn bag mechanism’ of small extracellular vesicle release via limiting membrane rupture of en bloc released amphisomes (amphiectosomes) |
| title_short | A ‘torn bag mechanism’ of small extracellular vesicle release via limiting membrane rupture of en bloc released amphisomes (amphiectosomes) |
| title_sort | torn bag mechanism of small extracellular vesicle release via limiting membrane rupture of en bloc released amphisomes amphiectosomes |
| topic | exosomes amphisome extracellular vesicles autophagy secretion biogenesis |
| url | https://elifesciences.org/articles/95828 |
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