Annexin A6 mediates calcium-dependent exosome secretion during plasma membrane repair
Exosomes are an extracellular vesicle (EV) subtype that is secreted upon the fusion of multivesicular bodies (MVBs) with the plasma membrane. Exosomes may participate in intercellular communication and have utility as disease biomarkers; however, little is known regarding the physiological stimuli t...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-05-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/86556 |
| _version_ | 1797810799538864128 |
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| author | Justin Krish Williams Jordan Matthew Ngo Isabelle Madeline Lehman Randy Schekman |
| author_facet | Justin Krish Williams Jordan Matthew Ngo Isabelle Madeline Lehman Randy Schekman |
| author_sort | Justin Krish Williams |
| collection | DOAJ |
| description | Exosomes are an extracellular vesicle (EV) subtype that is secreted upon the fusion of multivesicular bodies (MVBs) with the plasma membrane. Exosomes may participate in intercellular communication and have utility as disease biomarkers; however, little is known regarding the physiological stimuli that induce their secretion. Ca2+ influx promotes exosome secretion, raising the possibility that exosomes are secreted during the Ca2+-dependent plasma membrane repair of tissues damaged by mechanical stress in vivo. To determine whether exosomes are secreted upon plasma membrane damage, we developed sensitive assays to measure exosome secretion in intact and permeabilized cells. Our results suggest that exosome secretion is coupled to Ca2+-dependent plasma membrane repair. We find that annexin A6 (ANXA6), a well-known plasma membrane repair protein, is recruited to MVBs in the presence of Ca2+ and required for Ca2+-dependent exosome secretion, both in intact and in permeabilized cells. ANXA6 depletion stalls MVBs at the cell periphery, and ANXA6 truncations localize to different membranes, suggesting that ANXA6 may serve to tether MVBs to the plasma membrane. We find that cells secrete exosomes and other EVs upon plasma membrane damage and propose that repair-induced secretion may contribute to the pool of EVs present within biological fluids. |
| first_indexed | 2024-03-13T07:13:13Z |
| format | Article |
| id | doaj.art-b272ac02cd2f4df598da7a376408a7c9 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-13T07:13:13Z |
| publishDate | 2023-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-b272ac02cd2f4df598da7a376408a7c92023-06-05T14:55:13ZengeLife Sciences Publications LtdeLife2050-084X2023-05-011210.7554/eLife.86556Annexin A6 mediates calcium-dependent exosome secretion during plasma membrane repairJustin Krish Williams0https://orcid.org/0000-0002-9447-5554Jordan Matthew Ngo1https://orcid.org/0000-0002-6566-3919Isabelle Madeline Lehman2https://orcid.org/0009-0008-8667-401XRandy Schekman3https://orcid.org/0000-0001-8615-6409Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United StatesExosomes are an extracellular vesicle (EV) subtype that is secreted upon the fusion of multivesicular bodies (MVBs) with the plasma membrane. Exosomes may participate in intercellular communication and have utility as disease biomarkers; however, little is known regarding the physiological stimuli that induce their secretion. Ca2+ influx promotes exosome secretion, raising the possibility that exosomes are secreted during the Ca2+-dependent plasma membrane repair of tissues damaged by mechanical stress in vivo. To determine whether exosomes are secreted upon plasma membrane damage, we developed sensitive assays to measure exosome secretion in intact and permeabilized cells. Our results suggest that exosome secretion is coupled to Ca2+-dependent plasma membrane repair. We find that annexin A6 (ANXA6), a well-known plasma membrane repair protein, is recruited to MVBs in the presence of Ca2+ and required for Ca2+-dependent exosome secretion, both in intact and in permeabilized cells. ANXA6 depletion stalls MVBs at the cell periphery, and ANXA6 truncations localize to different membranes, suggesting that ANXA6 may serve to tether MVBs to the plasma membrane. We find that cells secrete exosomes and other EVs upon plasma membrane damage and propose that repair-induced secretion may contribute to the pool of EVs present within biological fluids.https://elifesciences.org/articles/86556exosomeextracellular vesicleplasma membrane repairannexin |
| spellingShingle | Justin Krish Williams Jordan Matthew Ngo Isabelle Madeline Lehman Randy Schekman Annexin A6 mediates calcium-dependent exosome secretion during plasma membrane repair eLife exosome extracellular vesicle plasma membrane repair annexin |
| title | Annexin A6 mediates calcium-dependent exosome secretion during plasma membrane repair |
| title_full | Annexin A6 mediates calcium-dependent exosome secretion during plasma membrane repair |
| title_fullStr | Annexin A6 mediates calcium-dependent exosome secretion during plasma membrane repair |
| title_full_unstemmed | Annexin A6 mediates calcium-dependent exosome secretion during plasma membrane repair |
| title_short | Annexin A6 mediates calcium-dependent exosome secretion during plasma membrane repair |
| title_sort | annexin a6 mediates calcium dependent exosome secretion during plasma membrane repair |
| topic | exosome extracellular vesicle plasma membrane repair annexin |
| url | https://elifesciences.org/articles/86556 |
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