Cyclin B Export to the Cytoplasm via the Nup62 Subcomplex and Subsequent Rapid Nuclear Import Are Required for the Initiation of <i>Drosophila</i> Male Meiosis
The cyclin-dependent kinase 1 (Cdk1)–cyclin B (CycB) complex plays critical roles in cell-cycle regulation. Before <i>Drosophila</i> male meiosis, CycB is exported from the nucleus to the cytoplasm via the nuclear porin 62kD (Nup62) subcomplex of the nuclear pore complex. When this expor...
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MDPI AG
2023-11-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/22/2611 |
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| author | Kanta Yamazoe Yoshihiro H. Inoue |
| author_facet | Kanta Yamazoe Yoshihiro H. Inoue |
| author_sort | Kanta Yamazoe |
| collection | DOAJ |
| description | The cyclin-dependent kinase 1 (Cdk1)–cyclin B (CycB) complex plays critical roles in cell-cycle regulation. Before <i>Drosophila</i> male meiosis, CycB is exported from the nucleus to the cytoplasm via the nuclear porin 62kD (Nup62) subcomplex of the nuclear pore complex. When this export is inhibited, Cdk1 is not activated, and meiosis does not initiate. We investigated the mechanism that controls the cellular localization and activation of Cdk1. Cdk1–CycB continuously shuttled into and out of the nucleus before meiosis. Overexpression of CycB, but not that of CycB with nuclear localization signal sequences, rescued reduced cytoplasmic CycB and inhibition of meiosis in <i>Nup62</i>-silenced cells. Full-scale Cdk1 activation occurred in the nucleus shortly after its rapid nuclear entry. Cdk1-dependent centrosome separation did not occur in <i>Nup62-</i>silenced cells, whereas Cdk1 interacted with Cdk-activating kinase and Twine/Cdc25C in the nuclei of <i>Nup62-</i>silenced cells, suggesting the involvement of another suppression mechanism. Silencing of <i>roughex</i> rescued Cdk1 inhibition and initiated meiosis. Nuclear export of Cdk1 ensured its escape from inhibition by a cyclin-dependent kinase inhibitor. The complex re-entered the nucleus via importin β at the onset of meiosis. We propose a model regarding the dynamics and activation mechanism of Cdk1–CycB to initiate male meiosis. |
| first_indexed | 2024-03-09T16:55:19Z |
| format | Article |
| id | doaj.art-0161e41bb1274588bb61c61f2f4d92df |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T16:55:19Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-0161e41bb1274588bb61c61f2f4d92df2023-11-24T14:35:16ZengMDPI AGCells2073-44092023-11-011222261110.3390/cells12222611Cyclin B Export to the Cytoplasm via the Nup62 Subcomplex and Subsequent Rapid Nuclear Import Are Required for the Initiation of <i>Drosophila</i> Male MeiosisKanta Yamazoe0Yoshihiro H. Inoue1Biomedical Research Center, Graduate School of Science and Technology, Kyoto Institute of Technology, Matsugasaki, Sakyo, Kyoto 606-0962, JapanBiomedical Research Center, Graduate School of Science and Technology, Kyoto Institute of Technology, Matsugasaki, Sakyo, Kyoto 606-0962, JapanThe cyclin-dependent kinase 1 (Cdk1)–cyclin B (CycB) complex plays critical roles in cell-cycle regulation. Before <i>Drosophila</i> male meiosis, CycB is exported from the nucleus to the cytoplasm via the nuclear porin 62kD (Nup62) subcomplex of the nuclear pore complex. When this export is inhibited, Cdk1 is not activated, and meiosis does not initiate. We investigated the mechanism that controls the cellular localization and activation of Cdk1. Cdk1–CycB continuously shuttled into and out of the nucleus before meiosis. Overexpression of CycB, but not that of CycB with nuclear localization signal sequences, rescued reduced cytoplasmic CycB and inhibition of meiosis in <i>Nup62</i>-silenced cells. Full-scale Cdk1 activation occurred in the nucleus shortly after its rapid nuclear entry. Cdk1-dependent centrosome separation did not occur in <i>Nup62-</i>silenced cells, whereas Cdk1 interacted with Cdk-activating kinase and Twine/Cdc25C in the nuclei of <i>Nup62-</i>silenced cells, suggesting the involvement of another suppression mechanism. Silencing of <i>roughex</i> rescued Cdk1 inhibition and initiated meiosis. Nuclear export of Cdk1 ensured its escape from inhibition by a cyclin-dependent kinase inhibitor. The complex re-entered the nucleus via importin β at the onset of meiosis. We propose a model regarding the dynamics and activation mechanism of Cdk1–CycB to initiate male meiosis.https://www.mdpi.com/2073-4409/12/22/2611<i>Drosophila</i>male meiosiscyclin Bcyclin-dependent kinase 1cyclin-dependent kinase inhibitor |
| spellingShingle | Kanta Yamazoe Yoshihiro H. Inoue Cyclin B Export to the Cytoplasm via the Nup62 Subcomplex and Subsequent Rapid Nuclear Import Are Required for the Initiation of <i>Drosophila</i> Male Meiosis Cells <i>Drosophila</i> male meiosis cyclin B cyclin-dependent kinase 1 cyclin-dependent kinase inhibitor |
| title | Cyclin B Export to the Cytoplasm via the Nup62 Subcomplex and Subsequent Rapid Nuclear Import Are Required for the Initiation of <i>Drosophila</i> Male Meiosis |
| title_full | Cyclin B Export to the Cytoplasm via the Nup62 Subcomplex and Subsequent Rapid Nuclear Import Are Required for the Initiation of <i>Drosophila</i> Male Meiosis |
| title_fullStr | Cyclin B Export to the Cytoplasm via the Nup62 Subcomplex and Subsequent Rapid Nuclear Import Are Required for the Initiation of <i>Drosophila</i> Male Meiosis |
| title_full_unstemmed | Cyclin B Export to the Cytoplasm via the Nup62 Subcomplex and Subsequent Rapid Nuclear Import Are Required for the Initiation of <i>Drosophila</i> Male Meiosis |
| title_short | Cyclin B Export to the Cytoplasm via the Nup62 Subcomplex and Subsequent Rapid Nuclear Import Are Required for the Initiation of <i>Drosophila</i> Male Meiosis |
| title_sort | cyclin b export to the cytoplasm via the nup62 subcomplex and subsequent rapid nuclear import are required for the initiation of i drosophila i male meiosis |
| topic | <i>Drosophila</i> male meiosis cyclin B cyclin-dependent kinase 1 cyclin-dependent kinase inhibitor |
| url | https://www.mdpi.com/2073-4409/12/22/2611 |
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