A survey of the specificity and mechanism of 1,6 hexanediol-induced disruption of nuclear transport
ABSTRACTSelective transport through the nuclear pore complex (NPC) depends on the dynamic binding of FG-repeat containing nucleoporins, the FG-nups, with each other and with Karyopherins (Kaps). Here, we assessed the specificity and mechanism by which the aliphatic alcohol 1,6-hexanediol (1,6HD) dis...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Nucleus |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19491034.2023.2240139 |
| _version_ | 1827580770674278400 |
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| author | Elizabeth C. Riquelme Barrientos Tegan A. Otto Sara N. Mouton Anton Steen Liesbeth M. Veenhoff |
| author_facet | Elizabeth C. Riquelme Barrientos Tegan A. Otto Sara N. Mouton Anton Steen Liesbeth M. Veenhoff |
| author_sort | Elizabeth C. Riquelme Barrientos |
| collection | DOAJ |
| description | ABSTRACTSelective transport through the nuclear pore complex (NPC) depends on the dynamic binding of FG-repeat containing nucleoporins, the FG-nups, with each other and with Karyopherins (Kaps). Here, we assessed the specificity and mechanism by which the aliphatic alcohol 1,6-hexanediol (1,6HD) disrupts the permeability barrier of NPCs in live baker’s yeast cells. After a 10-minute exposure to 5% 1,6HD, no notable changes were observed in cell growth, cytosolic pH and ATP levels, or the appearance of organelles. However, effects on the cytoskeleton and Hsp104 were noted. 1,6HD clearly affected the NPC permeability barrier, allowing passive nuclear entry of a 177kDa reporter protein that is normally confined to the cytosol. Moreover, multiple Kaps were displaced from NPCs, and the displacement of Kap122-GFP correlated with the observed passive permeability changes. 1,6HD thus temporarily permeates NPCs, and in line with Kap-centric models, the mechanism includes the release of numerous Kaps from the NPCs. |
| first_indexed | 2024-03-08T22:24:01Z |
| format | Article |
| id | doaj.art-f4a418bac2524a3cb62a9a4be4b2f47c |
| institution | Directory Open Access Journal |
| issn | 1949-1034 1949-1042 |
| language | English |
| last_indexed | 2024-03-08T22:24:01Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Nucleus |
| spelling | doaj.art-f4a418bac2524a3cb62a9a4be4b2f47c2023-12-18T11:21:33ZengTaylor & Francis GroupNucleus1949-10341949-10422023-12-0114110.1080/19491034.2023.2240139A survey of the specificity and mechanism of 1,6 hexanediol-induced disruption of nuclear transportElizabeth C. Riquelme Barrientos0Tegan A. Otto1Sara N. Mouton2Anton Steen3Liesbeth M. Veenhoff4European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, Groningen, The NetherlandsEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, Groningen, The NetherlandsEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, Groningen, The NetherlandsEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, Groningen, The NetherlandsEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, Groningen, The NetherlandsABSTRACTSelective transport through the nuclear pore complex (NPC) depends on the dynamic binding of FG-repeat containing nucleoporins, the FG-nups, with each other and with Karyopherins (Kaps). Here, we assessed the specificity and mechanism by which the aliphatic alcohol 1,6-hexanediol (1,6HD) disrupts the permeability barrier of NPCs in live baker’s yeast cells. After a 10-minute exposure to 5% 1,6HD, no notable changes were observed in cell growth, cytosolic pH and ATP levels, or the appearance of organelles. However, effects on the cytoskeleton and Hsp104 were noted. 1,6HD clearly affected the NPC permeability barrier, allowing passive nuclear entry of a 177kDa reporter protein that is normally confined to the cytosol. Moreover, multiple Kaps were displaced from NPCs, and the displacement of Kap122-GFP correlated with the observed passive permeability changes. 1,6HD thus temporarily permeates NPCs, and in line with Kap-centric models, the mechanism includes the release of numerous Kaps from the NPCs.https://www.tandfonline.com/doi/10.1080/19491034.2023.22401391,6-hexanediolaliphatic alcoholbaker’s yeastKaryopherinliquid-liquid phase separationNuclear pore complex |
| spellingShingle | Elizabeth C. Riquelme Barrientos Tegan A. Otto Sara N. Mouton Anton Steen Liesbeth M. Veenhoff A survey of the specificity and mechanism of 1,6 hexanediol-induced disruption of nuclear transport Nucleus 1,6-hexanediol aliphatic alcohol baker’s yeast Karyopherin liquid-liquid phase separation Nuclear pore complex |
| title | A survey of the specificity and mechanism of 1,6 hexanediol-induced disruption of nuclear transport |
| title_full | A survey of the specificity and mechanism of 1,6 hexanediol-induced disruption of nuclear transport |
| title_fullStr | A survey of the specificity and mechanism of 1,6 hexanediol-induced disruption of nuclear transport |
| title_full_unstemmed | A survey of the specificity and mechanism of 1,6 hexanediol-induced disruption of nuclear transport |
| title_short | A survey of the specificity and mechanism of 1,6 hexanediol-induced disruption of nuclear transport |
| title_sort | survey of the specificity and mechanism of 1 6 hexanediol induced disruption of nuclear transport |
| topic | 1,6-hexanediol aliphatic alcohol baker’s yeast Karyopherin liquid-liquid phase separation Nuclear pore complex |
| url | https://www.tandfonline.com/doi/10.1080/19491034.2023.2240139 |
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