Exportin-mediated nucleocytoplasmic transport maintains Pch2 homeostasis during meiosis.
The meiotic recombination checkpoint reinforces the order of events during meiotic prophase I, ensuring the accurate distribution of chromosomes to the gametes. The AAA+ ATPase Pch2 remodels the Hop1 axial protein enabling adequate levels of Hop1-T318 phosphorylation to support the ensuing checkpoin...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-11-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1011026 |
| _version_ | 1797389560916738048 |
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| author | Esther Herruzo Estefanía Sánchez-Díaz Sara González-Arranz Beatriz Santos Jesús A Carballo Pedro A San-Segundo |
| author_facet | Esther Herruzo Estefanía Sánchez-Díaz Sara González-Arranz Beatriz Santos Jesús A Carballo Pedro A San-Segundo |
| author_sort | Esther Herruzo |
| collection | DOAJ |
| description | The meiotic recombination checkpoint reinforces the order of events during meiotic prophase I, ensuring the accurate distribution of chromosomes to the gametes. The AAA+ ATPase Pch2 remodels the Hop1 axial protein enabling adequate levels of Hop1-T318 phosphorylation to support the ensuing checkpoint response. While these events are localized at chromosome axes, the checkpoint activating function of Pch2 relies on its cytoplasmic population. In contrast, forced nuclear accumulation of Pch2 leads to checkpoint inactivation. Here, we reveal the mechanism by which Pch2 travels from the cell nucleus to the cytoplasm to maintain Pch2 cellular homeostasis. Leptomycin B treatment provokes the nuclear accumulation of Pch2, indicating that its nucleocytoplasmic transport is mediated by the Crm1 exportin recognizing proteins containing Nuclear Export Signals (NESs). Consistently, leptomycin B leads to checkpoint inactivation and impaired Hop1 axial localization. Pch2 nucleocytoplasmic traffic is independent of its association with Zip1 and Orc1. We also identify a functional NES in the non-catalytic N-terminal domain of Pch2 that is required for its nucleocytoplasmic trafficking and proper checkpoint activity. In sum, we unveil another layer of control of Pch2 function during meiosis involving nuclear export via the exportin pathway that is crucial to maintain the critical balance of Pch2 distribution among different cellular compartments. |
| first_indexed | 2024-03-08T22:57:41Z |
| format | Article |
| id | doaj.art-9300ae190f1341c2bbea7e33019e69f9 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-03-08T22:57:41Z |
| publishDate | 2023-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-9300ae190f1341c2bbea7e33019e69f92023-12-16T05:31:31ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042023-11-011911e101102610.1371/journal.pgen.1011026Exportin-mediated nucleocytoplasmic transport maintains Pch2 homeostasis during meiosis.Esther HerruzoEstefanía Sánchez-DíazSara González-ArranzBeatriz SantosJesús A CarballoPedro A San-SegundoThe meiotic recombination checkpoint reinforces the order of events during meiotic prophase I, ensuring the accurate distribution of chromosomes to the gametes. The AAA+ ATPase Pch2 remodels the Hop1 axial protein enabling adequate levels of Hop1-T318 phosphorylation to support the ensuing checkpoint response. While these events are localized at chromosome axes, the checkpoint activating function of Pch2 relies on its cytoplasmic population. In contrast, forced nuclear accumulation of Pch2 leads to checkpoint inactivation. Here, we reveal the mechanism by which Pch2 travels from the cell nucleus to the cytoplasm to maintain Pch2 cellular homeostasis. Leptomycin B treatment provokes the nuclear accumulation of Pch2, indicating that its nucleocytoplasmic transport is mediated by the Crm1 exportin recognizing proteins containing Nuclear Export Signals (NESs). Consistently, leptomycin B leads to checkpoint inactivation and impaired Hop1 axial localization. Pch2 nucleocytoplasmic traffic is independent of its association with Zip1 and Orc1. We also identify a functional NES in the non-catalytic N-terminal domain of Pch2 that is required for its nucleocytoplasmic trafficking and proper checkpoint activity. In sum, we unveil another layer of control of Pch2 function during meiosis involving nuclear export via the exportin pathway that is crucial to maintain the critical balance of Pch2 distribution among different cellular compartments.https://doi.org/10.1371/journal.pgen.1011026 |
| spellingShingle | Esther Herruzo Estefanía Sánchez-Díaz Sara González-Arranz Beatriz Santos Jesús A Carballo Pedro A San-Segundo Exportin-mediated nucleocytoplasmic transport maintains Pch2 homeostasis during meiosis. PLoS Genetics |
| title | Exportin-mediated nucleocytoplasmic transport maintains Pch2 homeostasis during meiosis. |
| title_full | Exportin-mediated nucleocytoplasmic transport maintains Pch2 homeostasis during meiosis. |
| title_fullStr | Exportin-mediated nucleocytoplasmic transport maintains Pch2 homeostasis during meiosis. |
| title_full_unstemmed | Exportin-mediated nucleocytoplasmic transport maintains Pch2 homeostasis during meiosis. |
| title_short | Exportin-mediated nucleocytoplasmic transport maintains Pch2 homeostasis during meiosis. |
| title_sort | exportin mediated nucleocytoplasmic transport maintains pch2 homeostasis during meiosis |
| url | https://doi.org/10.1371/journal.pgen.1011026 |
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