VAMP5 and distinct sets of cognate Q-SNAREs mediate exosome release
Small extracellular vesicles (sEVs) are largely classified into two types, plasma-membrane derived sEVs and endomembrane-derived sEVs. The latter type (referred to as exosomes herein) is originated from late endosomes or multivesicular bodies (MVBs). In order to release exosomes extracellularly, MVB...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Japan Society for Cell Biology
2023-09-01
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| Series: | Cell Structure and Function |
| Subjects: | |
| Online Access: | https://www.jstage.jst.go.jp/article/csf/48/2/48_23067/_html/-char/en |
| _version_ | 1797643463543488512 |
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| author | Takahide Matsui Yuriko Sakamaki Shu Hiragi Mitsunori Fukuda |
| author_facet | Takahide Matsui Yuriko Sakamaki Shu Hiragi Mitsunori Fukuda |
| author_sort | Takahide Matsui |
| collection | DOAJ |
| description | Small extracellular vesicles (sEVs) are largely classified into two types, plasma-membrane derived sEVs and endomembrane-derived sEVs. The latter type (referred to as exosomes herein) is originated from late endosomes or multivesicular bodies (MVBs). In order to release exosomes extracellularly, MVBs must fuse with the plasma membrane, not with lysosomes. In contrast to the mechanism responsible for MVB–lysosome fusion, the mechanism underlying the MVB–plasma membrane fusion is poorly understood. Here, we systematically analyze soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) family proteins and identify VAMP5 as an MVB-localized SNARE protein required for exosome release. Depletion of VAMP5 in HeLa cells impairs exosome release. Mechanistically, VAMP5 mediates exosome release by interacting with SNAP47 and plasma membrane SNARE Syntaxin 1 (STX1) or STX4 to release exosomes. VAMP5 is also found to mediate asymmetric exosome release from polarized Madin-Darby canine kidney (MDCK) epithelial cells through interaction with the distinct sets of Q-SNAREs, suggesting that VAMP5 is a general exosome regulator in both polarized cells and non-polarized cells. Key words: exosome, small extracellular vesicle (sEV), multivesicular body, SNARE, VAMP5 |
| first_indexed | 2024-03-11T14:15:11Z |
| format | Article |
| id | doaj.art-6141434ccd734b0dbefadf0b10cc1bbd |
| institution | Directory Open Access Journal |
| issn | 0386-7196 1347-3700 |
| language | English |
| last_indexed | 2024-03-11T14:15:11Z |
| publishDate | 2023-09-01 |
| publisher | Japan Society for Cell Biology |
| record_format | Article |
| series | Cell Structure and Function |
| spelling | doaj.art-6141434ccd734b0dbefadf0b10cc1bbd2023-11-01T07:09:45ZengJapan Society for Cell BiologyCell Structure and Function0386-71961347-37002023-09-0148218719810.1247/csf.23067csfVAMP5 and distinct sets of cognate Q-SNAREs mediate exosome releaseTakahide Matsui0Yuriko Sakamaki1Shu Hiragi2Mitsunori Fukuda3Laboratory of Membrane Trafficking Mechanisms, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku UniversityMicroscopy Research Support Unit Research Core, Tokyo Medical and Dental UniversityLaboratory of Membrane Trafficking Mechanisms, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku UniversityLaboratory of Membrane Trafficking Mechanisms, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku UniversitySmall extracellular vesicles (sEVs) are largely classified into two types, plasma-membrane derived sEVs and endomembrane-derived sEVs. The latter type (referred to as exosomes herein) is originated from late endosomes or multivesicular bodies (MVBs). In order to release exosomes extracellularly, MVBs must fuse with the plasma membrane, not with lysosomes. In contrast to the mechanism responsible for MVB–lysosome fusion, the mechanism underlying the MVB–plasma membrane fusion is poorly understood. Here, we systematically analyze soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) family proteins and identify VAMP5 as an MVB-localized SNARE protein required for exosome release. Depletion of VAMP5 in HeLa cells impairs exosome release. Mechanistically, VAMP5 mediates exosome release by interacting with SNAP47 and plasma membrane SNARE Syntaxin 1 (STX1) or STX4 to release exosomes. VAMP5 is also found to mediate asymmetric exosome release from polarized Madin-Darby canine kidney (MDCK) epithelial cells through interaction with the distinct sets of Q-SNAREs, suggesting that VAMP5 is a general exosome regulator in both polarized cells and non-polarized cells. Key words: exosome, small extracellular vesicle (sEV), multivesicular body, SNARE, VAMP5https://www.jstage.jst.go.jp/article/csf/48/2/48_23067/_html/-char/enexosomesmall extracellular vesicle (sev)multivesicular bodysnarevamp5 |
| spellingShingle | Takahide Matsui Yuriko Sakamaki Shu Hiragi Mitsunori Fukuda VAMP5 and distinct sets of cognate Q-SNAREs mediate exosome release Cell Structure and Function exosome small extracellular vesicle (sev) multivesicular body snare vamp5 |
| title | VAMP5 and distinct sets of cognate Q-SNAREs mediate exosome release |
| title_full | VAMP5 and distinct sets of cognate Q-SNAREs mediate exosome release |
| title_fullStr | VAMP5 and distinct sets of cognate Q-SNAREs mediate exosome release |
| title_full_unstemmed | VAMP5 and distinct sets of cognate Q-SNAREs mediate exosome release |
| title_short | VAMP5 and distinct sets of cognate Q-SNAREs mediate exosome release |
| title_sort | vamp5 and distinct sets of cognate q snares mediate exosome release |
| topic | exosome small extracellular vesicle (sev) multivesicular body snare vamp5 |
| url | https://www.jstage.jst.go.jp/article/csf/48/2/48_23067/_html/-char/en |
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