TPPP acts downstream of RhoA-ROCK-LIMK2 to regulate astral microtubule organization and spindle orientation
The actin cytoskeleton in eukaryotic cells undergoes drastic rearrangement during mitosis. The changes to the actin cytoskeleton are most obvious in the adherent cells, where the actin stress fibres are disassembled, and the cortical actin network becomes more prominent with concomitant increase in...
| Main Authors: | , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2014
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| Online Access: | https://hdl.handle.net/10356/101516 http://hdl.handle.net/10220/18676 |
| _version_ | 1824453562089865216 |
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| author | Heng, Yi-Wen. Lim, Hong-Hwa. Mina, Theresia. Utomo, Prayudi. Zhong, Shaoping. Lim, Chwee-Teck. Koh, Cheng-Gee |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Heng, Yi-Wen. Lim, Hong-Hwa. Mina, Theresia. Utomo, Prayudi. Zhong, Shaoping. Lim, Chwee-Teck. Koh, Cheng-Gee |
| author_sort | Heng, Yi-Wen. |
| collection | NTU |
| description | The actin cytoskeleton in eukaryotic cells undergoes drastic rearrangement during mitosis. The changes to the actin cytoskeleton are most obvious in the adherent cells, where the actin stress fibres are disassembled, and the cortical actin network becomes more prominent with concomitant increase in cell rigidity as cells round up and enter mitosis. Although the regulatory connections between the actin cytoskeleton and the early mitotic events are apparent, the mechanisms that govern these links are not well understood. Here, we report that LIMK1 and LIMK2, the downstream effectors of RhoA and ROCK, regulate centrosome integrity and astral microtubule organization, respectively. Surprisingly, LIMK1 and cofilin are not involved downstream of RhoA and ROCK in the regulation of astral microtubule organization. Instead, we find that LIMK2 acts through TPPP in the regulation of astral microtubule organization, whereas both LIMK1 and LIMK2 affect centrosome focusing. Both phenotypes are tightly coupled to spindle orientation in the mitotic cells. Thus, our results reveal a new regulatory link between the actin cytoskeleton and the mitotic spindle during the early stages of mitosis. |
| first_indexed | 2025-02-19T03:08:23Z |
| format | Journal Article |
| id | ntu-10356/101516 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:08:23Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | ntu-10356/1015162023-02-28T17:04:57Z TPPP acts downstream of RhoA-ROCK-LIMK2 to regulate astral microtubule organization and spindle orientation Heng, Yi-Wen. Lim, Hong-Hwa. Mina, Theresia. Utomo, Prayudi. Zhong, Shaoping. Lim, Chwee-Teck. Koh, Cheng-Gee School of Biological Sciences DRNTU::Science::Biological sciences The actin cytoskeleton in eukaryotic cells undergoes drastic rearrangement during mitosis. The changes to the actin cytoskeleton are most obvious in the adherent cells, where the actin stress fibres are disassembled, and the cortical actin network becomes more prominent with concomitant increase in cell rigidity as cells round up and enter mitosis. Although the regulatory connections between the actin cytoskeleton and the early mitotic events are apparent, the mechanisms that govern these links are not well understood. Here, we report that LIMK1 and LIMK2, the downstream effectors of RhoA and ROCK, regulate centrosome integrity and astral microtubule organization, respectively. Surprisingly, LIMK1 and cofilin are not involved downstream of RhoA and ROCK in the regulation of astral microtubule organization. Instead, we find that LIMK2 acts through TPPP in the regulation of astral microtubule organization, whereas both LIMK1 and LIMK2 affect centrosome focusing. Both phenotypes are tightly coupled to spindle orientation in the mitotic cells. Thus, our results reveal a new regulatory link between the actin cytoskeleton and the mitotic spindle during the early stages of mitosis. Published version 2014-01-22T03:44:22Z 2019-12-06T20:39:40Z 2014-01-22T03:44:22Z 2019-12-06T20:39:40Z 2012 2012 Journal Article Heng, Y.-W., Lim, H.-H., Mina, T., Utomo, P., Zhong, S., Lim, C.-T., et al. (2012). TPPP acts downstream of RhoA-ROCK-LIMK2 to regulate astral microtubule organization and spindle orientation. Journal of cell science, 125(6), 1579-1590. https://hdl.handle.net/10356/101516 http://hdl.handle.net/10220/18676 10.1242/jcs.096818 en Journal of cell science © 2012 The Authors. This paper was published in Journal of Cell Science and is made available as an electronic reprint (preprint) with permission of the authors. The paper can be found at the following official DOI: [http://dx.doi.org/10.1242/jcs.096818]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences Heng, Yi-Wen. Lim, Hong-Hwa. Mina, Theresia. Utomo, Prayudi. Zhong, Shaoping. Lim, Chwee-Teck. Koh, Cheng-Gee TPPP acts downstream of RhoA-ROCK-LIMK2 to regulate astral microtubule organization and spindle orientation |
| title | TPPP acts downstream of RhoA-ROCK-LIMK2 to regulate astral microtubule organization and spindle orientation |
| title_full | TPPP acts downstream of RhoA-ROCK-LIMK2 to regulate astral microtubule organization and spindle orientation |
| title_fullStr | TPPP acts downstream of RhoA-ROCK-LIMK2 to regulate astral microtubule organization and spindle orientation |
| title_full_unstemmed | TPPP acts downstream of RhoA-ROCK-LIMK2 to regulate astral microtubule organization and spindle orientation |
| title_short | TPPP acts downstream of RhoA-ROCK-LIMK2 to regulate astral microtubule organization and spindle orientation |
| title_sort | tppp acts downstream of rhoa rock limk2 to regulate astral microtubule organization and spindle orientation |
| topic | DRNTU::Science::Biological sciences |
| url | https://hdl.handle.net/10356/101516 http://hdl.handle.net/10220/18676 |
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