Phosphatidylinositol-5-phosphate 4-kinase gamma accumulates at the spindle pole and prevents microtubule depolymerization
Abstract Background A previous screen of a human kinase and phosphatase shRNA library to select genes that mediate arsenite induction of spindle abnormalities resulted in the identification of phosphatidylinositol-5-phosphate 4-kinase type-2 gamma (PIP4KIIγ), a phosphatidylinositol 4,5-bisphosphate...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-08-01
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| Series: | Cell Division |
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| Online Access: | http://link.springer.com/article/10.1186/s13008-019-0053-9 |
| _version_ | 1818835951201288192 |
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| author | Tz-Chi Lin Hsiao-Hui Kuo Yi-Chen Wu Tiffany S. Pan Ling-Huei Yih |
| author_facet | Tz-Chi Lin Hsiao-Hui Kuo Yi-Chen Wu Tiffany S. Pan Ling-Huei Yih |
| author_sort | Tz-Chi Lin |
| collection | DOAJ |
| description | Abstract Background A previous screen of a human kinase and phosphatase shRNA library to select genes that mediate arsenite induction of spindle abnormalities resulted in the identification of phosphatidylinositol-5-phosphate 4-kinase type-2 gamma (PIP4KIIγ), a phosphatidylinositol 4,5-bisphosphate (PIP2)-synthesizing enzyme. In this study, we explored how PIP4KIIγ regulates the assembly of mitotic spindles. Results PIP4KIIγ accumulates at the spindle pole before anaphase, and is required for the assembly of functional bipolar spindles. Depletion of PIP4KIIγ enhanced the spindle pole accumulation of mitotic centromere-associated kinesin (MCAK), a microtubule (MT)-depolymerizing kinesin, and resulted in a less stable spindle pole-associated MT. Depletion of MCAK can ameliorate PIP4KIIγ depletion-induced spindle abnormalities. In addition, PIP2 binds to polo-like kinase (PLK1) and reduces PLK1-mediated phosphorylation of MCAK. These results indicate that PIP4KIIγ and PIP2 may negatively regulate the MT depolymerization activity of MCAK by reducing PLK1-mediated phosphorylation of MCAK. Consequently, depletion of PLK1 has been shown to counteract the PIP4KIIγ depletion-induced instability of spindle pole-associated MT and cell resistance to arsenite. Conclusions Our current results imply that PIP4KIIγ may restrain MT depolymerization at the spindle pole through attenuating PLK1-mediated activation of MCAK before anaphase onset. |
| first_indexed | 2024-12-19T02:58:52Z |
| format | Article |
| id | doaj.art-4a2fe16d877c46418914d6e853a0ece3 |
| institution | Directory Open Access Journal |
| issn | 1747-1028 |
| language | English |
| last_indexed | 2024-12-19T02:58:52Z |
| publishDate | 2019-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Division |
| spelling | doaj.art-4a2fe16d877c46418914d6e853a0ece32022-12-21T20:38:16ZengBMCCell Division1747-10282019-08-0114111410.1186/s13008-019-0053-9Phosphatidylinositol-5-phosphate 4-kinase gamma accumulates at the spindle pole and prevents microtubule depolymerizationTz-Chi Lin0Hsiao-Hui Kuo1Yi-Chen Wu2Tiffany S. Pan3Ling-Huei Yih4Institute of Cellular and Organismic Biology, Academia SinicaInstitute of Cellular and Organismic Biology, Academia SinicaInstitute of Cellular and Organismic Biology, Academia SinicaInstitute of Cellular and Organismic Biology, Academia SinicaInstitute of Cellular and Organismic Biology, Academia SinicaAbstract Background A previous screen of a human kinase and phosphatase shRNA library to select genes that mediate arsenite induction of spindle abnormalities resulted in the identification of phosphatidylinositol-5-phosphate 4-kinase type-2 gamma (PIP4KIIγ), a phosphatidylinositol 4,5-bisphosphate (PIP2)-synthesizing enzyme. In this study, we explored how PIP4KIIγ regulates the assembly of mitotic spindles. Results PIP4KIIγ accumulates at the spindle pole before anaphase, and is required for the assembly of functional bipolar spindles. Depletion of PIP4KIIγ enhanced the spindle pole accumulation of mitotic centromere-associated kinesin (MCAK), a microtubule (MT)-depolymerizing kinesin, and resulted in a less stable spindle pole-associated MT. Depletion of MCAK can ameliorate PIP4KIIγ depletion-induced spindle abnormalities. In addition, PIP2 binds to polo-like kinase (PLK1) and reduces PLK1-mediated phosphorylation of MCAK. These results indicate that PIP4KIIγ and PIP2 may negatively regulate the MT depolymerization activity of MCAK by reducing PLK1-mediated phosphorylation of MCAK. Consequently, depletion of PLK1 has been shown to counteract the PIP4KIIγ depletion-induced instability of spindle pole-associated MT and cell resistance to arsenite. Conclusions Our current results imply that PIP4KIIγ may restrain MT depolymerization at the spindle pole through attenuating PLK1-mediated activation of MCAK before anaphase onset.http://link.springer.com/article/10.1186/s13008-019-0053-9Mitotic centromere-associated kinesin (MCAK)Microtubule depolymerizationPhosphatidylinositol 4,5-bisphosphate (PIP2)Phosphatidylinositol 5-phosphate 4-kinase type II gamma (PIP4KIIγ)Polo-like kinase (PLK1)Spindle pole |
| spellingShingle | Tz-Chi Lin Hsiao-Hui Kuo Yi-Chen Wu Tiffany S. Pan Ling-Huei Yih Phosphatidylinositol-5-phosphate 4-kinase gamma accumulates at the spindle pole and prevents microtubule depolymerization Cell Division Mitotic centromere-associated kinesin (MCAK) Microtubule depolymerization Phosphatidylinositol 4,5-bisphosphate (PIP2) Phosphatidylinositol 5-phosphate 4-kinase type II gamma (PIP4KIIγ) Polo-like kinase (PLK1) Spindle pole |
| title | Phosphatidylinositol-5-phosphate 4-kinase gamma accumulates at the spindle pole and prevents microtubule depolymerization |
| title_full | Phosphatidylinositol-5-phosphate 4-kinase gamma accumulates at the spindle pole and prevents microtubule depolymerization |
| title_fullStr | Phosphatidylinositol-5-phosphate 4-kinase gamma accumulates at the spindle pole and prevents microtubule depolymerization |
| title_full_unstemmed | Phosphatidylinositol-5-phosphate 4-kinase gamma accumulates at the spindle pole and prevents microtubule depolymerization |
| title_short | Phosphatidylinositol-5-phosphate 4-kinase gamma accumulates at the spindle pole and prevents microtubule depolymerization |
| title_sort | phosphatidylinositol 5 phosphate 4 kinase gamma accumulates at the spindle pole and prevents microtubule depolymerization |
| topic | Mitotic centromere-associated kinesin (MCAK) Microtubule depolymerization Phosphatidylinositol 4,5-bisphosphate (PIP2) Phosphatidylinositol 5-phosphate 4-kinase type II gamma (PIP4KIIγ) Polo-like kinase (PLK1) Spindle pole |
| url | http://link.springer.com/article/10.1186/s13008-019-0053-9 |
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