V-ATPase V0a1 promotes Weibel–Palade body biogenesis through the regulation of membrane fission
Membrane fission, the division of a membrane-bound structure into two discrete compartments, is essential for diverse cellular events, such as endocytosis and vesicle/granule biogenesis; however, the process remains unclear. The hemostatic protein von Willebrand factor is produced in vascular endoth...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-12-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/71526 |
| _version_ | 1811253617198366720 |
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| author | Yasuo Yamazaki Yuka Eura Koichi Kokame |
| author_facet | Yasuo Yamazaki Yuka Eura Koichi Kokame |
| author_sort | Yasuo Yamazaki |
| collection | DOAJ |
| description | Membrane fission, the division of a membrane-bound structure into two discrete compartments, is essential for diverse cellular events, such as endocytosis and vesicle/granule biogenesis; however, the process remains unclear. The hemostatic protein von Willebrand factor is produced in vascular endothelial cells and packaged into specialized secretory granules, Weibel–Palade bodies (WPBs) at the trans-Golgi network (TGN). Here, we reported that V0a1, a V-ATPase component, is required for the membrane fission of WPBs. We identified two V0a isoforms in distinct populations of WPBs in cultured endothelial cells, V0a1 and V0a2, on mature and nascent WPBs, respectively. Although WPB buds were formed, WPBs could not separate from the TGN in the absence of V0a1. Screening using dominant–negative forms of known membrane fission regulators revealed protein kinase D (PKD) as an essential factor in biogenesis of WPBs. Further, we showed that the induction of wild-type PKDs in V0a1-depleted cells does not support the segregation of WPBs from the TGN; suggesting a primary role of V0a1 in the membrane fission of WPBs. The identification of V0a1 as a new membrane fission regulator should facilitate the understanding of molecular events that enable membrane fission. |
| first_indexed | 2024-04-12T16:54:11Z |
| format | Article |
| id | doaj.art-de5a409f66384711870d8dfbe0a26836 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:54:11Z |
| publishDate | 2021-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-de5a409f66384711870d8dfbe0a268362022-12-22T03:24:18ZengeLife Sciences Publications LtdeLife2050-084X2021-12-011010.7554/eLife.71526V-ATPase V0a1 promotes Weibel–Palade body biogenesis through the regulation of membrane fissionYasuo Yamazaki0https://orcid.org/0000-0001-5297-9837Yuka Eura1https://orcid.org/0000-0001-5784-6339Koichi Kokame2https://orcid.org/0000-0002-9654-6299Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Osaka, JapanDepartment of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Osaka, JapanDepartment of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Osaka, JapanMembrane fission, the division of a membrane-bound structure into two discrete compartments, is essential for diverse cellular events, such as endocytosis and vesicle/granule biogenesis; however, the process remains unclear. The hemostatic protein von Willebrand factor is produced in vascular endothelial cells and packaged into specialized secretory granules, Weibel–Palade bodies (WPBs) at the trans-Golgi network (TGN). Here, we reported that V0a1, a V-ATPase component, is required for the membrane fission of WPBs. We identified two V0a isoforms in distinct populations of WPBs in cultured endothelial cells, V0a1 and V0a2, on mature and nascent WPBs, respectively. Although WPB buds were formed, WPBs could not separate from the TGN in the absence of V0a1. Screening using dominant–negative forms of known membrane fission regulators revealed protein kinase D (PKD) as an essential factor in biogenesis of WPBs. Further, we showed that the induction of wild-type PKDs in V0a1-depleted cells does not support the segregation of WPBs from the TGN; suggesting a primary role of V0a1 in the membrane fission of WPBs. The identification of V0a1 as a new membrane fission regulator should facilitate the understanding of molecular events that enable membrane fission.https://elifesciences.org/articles/71526hemostasisorganellegenesismembrane transportmembrane fission |
| spellingShingle | Yasuo Yamazaki Yuka Eura Koichi Kokame V-ATPase V0a1 promotes Weibel–Palade body biogenesis through the regulation of membrane fission eLife hemostasis organellegenesis membrane transport membrane fission |
| title | V-ATPase V0a1 promotes Weibel–Palade body biogenesis through the regulation of membrane fission |
| title_full | V-ATPase V0a1 promotes Weibel–Palade body biogenesis through the regulation of membrane fission |
| title_fullStr | V-ATPase V0a1 promotes Weibel–Palade body biogenesis through the regulation of membrane fission |
| title_full_unstemmed | V-ATPase V0a1 promotes Weibel–Palade body biogenesis through the regulation of membrane fission |
| title_short | V-ATPase V0a1 promotes Weibel–Palade body biogenesis through the regulation of membrane fission |
| title_sort | v atpase v0a1 promotes weibel palade body biogenesis through the regulation of membrane fission |
| topic | hemostasis organellegenesis membrane transport membrane fission |
| url | https://elifesciences.org/articles/71526 |
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