Taxol acts differently on different tubulin isotypes
Abstract Taxol is a small molecule effector that allosterically locks tubulin into the microtubule lattice. We show here that taxol has different effects on different single-isotype microtubule lattices. Using in vitro reconstitution, we demonstrate that single-isotype α1β4 GDP-tubulin lattices are...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05306-y |
| _version_ | 1797557167456256000 |
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| author | Yean Ming Chew Robert A. Cross |
| author_facet | Yean Ming Chew Robert A. Cross |
| author_sort | Yean Ming Chew |
| collection | DOAJ |
| description | Abstract Taxol is a small molecule effector that allosterically locks tubulin into the microtubule lattice. We show here that taxol has different effects on different single-isotype microtubule lattices. Using in vitro reconstitution, we demonstrate that single-isotype α1β4 GDP-tubulin lattices are stabilised and expanded by 10 µM taxol, as reported by accelerated microtubule gliding in kinesin motility assays, whereas single-isotype α1β3 GDP-tubulin lattices are stabilised but not expanded. This isotype-specific action of taxol drives gliding of segmented-isotype GDP-taxol microtubules along convoluted, sinusoidal paths, because their expanded α1β4 segments try to glide faster than their compacted α1β3 segments. In GMPCPP, single-isotype α1β3 and α1β4 lattices both show accelerated gliding, indicating that both can in principle be driven to expand. We therefore propose that taxol-induced lattice expansion requires a higher taxol occupancy than taxol-induced stabilisation, and that higher taxol occupancies are accessible to α1β4 but not α1β3 single-isotype lattices. |
| first_indexed | 2024-03-10T17:13:30Z |
| format | Article |
| id | doaj.art-c66b6eabede4475daaa507fc7552cd28 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-10T17:13:30Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-c66b6eabede4475daaa507fc7552cd282023-11-20T10:36:21ZengNature PortfolioCommunications Biology2399-36422023-09-016111510.1038/s42003-023-05306-yTaxol acts differently on different tubulin isotypesYean Ming Chew0Robert A. Cross1Centre for Mechanochemical Cell Biology, Warwick Medical SchoolCentre for Mechanochemical Cell Biology, Warwick Medical SchoolAbstract Taxol is a small molecule effector that allosterically locks tubulin into the microtubule lattice. We show here that taxol has different effects on different single-isotype microtubule lattices. Using in vitro reconstitution, we demonstrate that single-isotype α1β4 GDP-tubulin lattices are stabilised and expanded by 10 µM taxol, as reported by accelerated microtubule gliding in kinesin motility assays, whereas single-isotype α1β3 GDP-tubulin lattices are stabilised but not expanded. This isotype-specific action of taxol drives gliding of segmented-isotype GDP-taxol microtubules along convoluted, sinusoidal paths, because their expanded α1β4 segments try to glide faster than their compacted α1β3 segments. In GMPCPP, single-isotype α1β3 and α1β4 lattices both show accelerated gliding, indicating that both can in principle be driven to expand. We therefore propose that taxol-induced lattice expansion requires a higher taxol occupancy than taxol-induced stabilisation, and that higher taxol occupancies are accessible to α1β4 but not α1β3 single-isotype lattices.https://doi.org/10.1038/s42003-023-05306-y |
| spellingShingle | Yean Ming Chew Robert A. Cross Taxol acts differently on different tubulin isotypes Communications Biology |
| title | Taxol acts differently on different tubulin isotypes |
| title_full | Taxol acts differently on different tubulin isotypes |
| title_fullStr | Taxol acts differently on different tubulin isotypes |
| title_full_unstemmed | Taxol acts differently on different tubulin isotypes |
| title_short | Taxol acts differently on different tubulin isotypes |
| title_sort | taxol acts differently on different tubulin isotypes |
| url | https://doi.org/10.1038/s42003-023-05306-y |
| work_keys_str_mv | AT yeanmingchew taxolactsdifferentlyondifferenttubulinisotypes AT robertacross taxolactsdifferentlyondifferenttubulinisotypes |